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PROFESSOR: Maybe
I should go over

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00:00:27,210 --> 00:00:29,350
real quickly what
we did on Monday.

10
00:00:30,460 --> 00:00:34,540
We can start out with we
covered the various parts

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00:00:34,540 --> 00:00:39,060
of the auditory periphery--
the external, middle,

12
00:00:39,060 --> 00:00:39,935
and inner ears.

13
00:00:41,560 --> 00:00:46,430
And we had a paper on the
function of the external ear

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00:00:46,430 --> 00:00:52,040
and how it can help you localize
sounds when you distort it

15
00:00:52,040 --> 00:00:56,435
by using clay molds that you
can put in subjects' pinnae.

16
00:00:57,660 --> 00:00:59,930
Your sense of
localization of sounds,

17
00:00:59,930 --> 00:01:04,099
especially those at different
elevation, is all screwed up.

18
00:01:05,459 --> 00:01:08,140
And you can relearn
because you still

19
00:01:08,140 --> 00:01:12,880
have some bends and quirky
geometry in your pinnae.

20
00:01:12,880 --> 00:01:14,300
Even with a little
clay in there,

21
00:01:14,300 --> 00:01:19,770
you can relearn using new
clues to localize sounds

22
00:01:19,770 --> 00:01:21,880
in elevation, but it takes
a little bit of time.

23
00:01:21,880 --> 00:01:25,630
So the subjects in
that paper relearned

24
00:01:25,630 --> 00:01:26,870
how to localize sounds.

25
00:01:26,870 --> 00:01:28,460
Now, there are other
cues that we'll

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00:01:28,460 --> 00:01:32,060
be dealing with for localization
of sounds in azimuth.

27
00:01:32,060 --> 00:01:33,945
And that's where you
use two separate ears.

28
00:01:35,130 --> 00:01:38,390
For example, if a
sound's off to my right,

29
00:01:38,390 --> 00:01:41,170
it's going to hit
my right ear first.

30
00:01:41,170 --> 00:01:45,500
And then because sound travels
at a finite velocity in air,

31
00:01:45,500 --> 00:01:47,050
it's going to hit
my left ear second.

32
00:01:47,050 --> 00:01:50,310
So there's a delay
between the two ears,

33
00:01:50,310 --> 00:01:55,370
and that's a primary cue
for localizing in azimuth,

34
00:01:55,370 --> 00:01:56,620
in the horizontal plane.

35
00:01:58,500 --> 00:02:02,420
So one comment I
had after class was

36
00:02:02,420 --> 00:02:04,860
that was a good
paper on relearning

37
00:02:04,860 --> 00:02:06,790
sound localization
with new ears.

38
00:02:06,790 --> 00:02:08,680
Someone came up
and said they had

39
00:02:08,680 --> 00:02:10,360
read that in another
discussion group.

40
00:02:10,360 --> 00:02:12,030
And I think it is
a very good paper,

41
00:02:12,030 --> 00:02:14,800
because it deals with the
function of the external ear.

42
00:02:14,800 --> 00:02:18,050
It deals with how you
can relearn new cues.

43
00:02:18,050 --> 00:02:22,100
Let's say if when you grow up,
your pinnae are getting bigger

44
00:02:22,100 --> 00:02:23,980
from being an
infant to an adult.

45
00:02:23,980 --> 00:02:27,280
So you have to relearn
those cues over time.

46
00:02:29,090 --> 00:02:31,590
We talked about the
function of the middle ear,

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00:02:31,590 --> 00:02:34,600
securing efficient
transmission of sound energy

48
00:02:34,600 --> 00:02:37,230
from air into the
fluid of the inner ear.

49
00:02:39,390 --> 00:02:44,160
And we talked about, of course,
the physical characteristics

50
00:02:44,160 --> 00:02:48,890
of sound, what sound frequency
is, what sound level is.

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00:02:48,890 --> 00:02:50,770
We talked about
simple sounds-- that

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00:02:50,770 --> 00:02:52,890
is, pure tones or
single frequencies.

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00:02:53,970 --> 00:02:57,100
More complex sounds
like musical sounds that

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00:02:57,100 --> 00:03:00,890
have a bunch of
frequencies, and even speech

55
00:03:00,890 --> 00:03:04,740
sounds that have a whole
bunch of different frequencies

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00:03:04,740 --> 00:03:07,180
and they're changed
a little bit.

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00:03:07,180 --> 00:03:10,180
And the change is very
perceptually obvious

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00:03:10,180 --> 00:03:14,200
in the form of changing from
one vowel to another vowel.

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00:03:15,840 --> 00:03:20,004
And so another comment I got
by email, someone said, well,

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00:03:20,004 --> 00:03:21,420
can you tell me
where you're from?

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00:03:21,420 --> 00:03:23,445
Because you have a
Midwestern accent.

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00:03:24,620 --> 00:03:27,020
OK, speaking of speech sounds.

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00:03:27,020 --> 00:03:29,300
And that's a very
interesting comment,

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00:03:29,300 --> 00:03:33,660
because I've been in the
Boston area since 1983.

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00:03:33,660 --> 00:03:35,340
And that's 30 years.

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00:03:35,340 --> 00:03:38,620
And I am from the Midwest.

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00:03:38,620 --> 00:03:41,310
In fact, I brought my
Midwestern clothes today.

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00:03:41,310 --> 00:03:45,610
I got my hat and my
Michigan sweatshirt

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00:03:45,610 --> 00:03:47,890
which I got out of the rag pile.

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00:03:47,890 --> 00:03:49,380
Or is it my Harvard sweatshirt?

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00:03:49,380 --> 00:03:50,360
Let's see.

72
00:03:50,360 --> 00:03:53,096
It says, "Harvard,
Michigan of the East."

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00:03:53,096 --> 00:03:54,720
So I guess it's my
Michigan sweatshirt.

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00:03:54,720 --> 00:03:58,075
It's got the Michigan
colors, maize and blue.

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00:03:59,080 --> 00:04:01,540
And so I grew up in
Ann Arbor, Michigan.

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00:04:01,540 --> 00:04:04,030
I probably-- it
depends on who you are,

77
00:04:04,030 --> 00:04:06,050
you have to sort
of listen for it.

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00:04:06,050 --> 00:04:09,770
According to my wife I still
have it, and maybe some of you

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00:04:09,770 --> 00:04:11,940
can hear my Midwestern twang.

80
00:04:11,940 --> 00:04:16,329
So it's an evidence that
you have very good hearing

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00:04:16,329 --> 00:04:18,640
that you can hear these
different not only vowels

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00:04:18,640 --> 00:04:19,950
but accents.

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00:04:19,950 --> 00:04:22,860
So that's kind of
interesting that I

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00:04:22,860 --> 00:04:25,980
was reading a book
just last week.

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00:04:25,980 --> 00:04:27,530
And it's called Our Boston.

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00:04:27,530 --> 00:04:29,840
You can get at the MIT COOP.

87
00:04:29,840 --> 00:04:35,220
And one of the chapters
is on regional accents.

88
00:04:35,220 --> 00:04:38,740
And I'll do a
little reading maybe

89
00:04:38,740 --> 00:04:41,630
just at the very beginning
of this chapter which

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00:04:41,630 --> 00:04:44,480
talks about regional
accents and linguists.

91
00:04:44,480 --> 00:04:46,295
I'll just read you
the first sentence.

92
00:04:46,295 --> 00:04:50,130
It says, "As most
linguists might tell you,

93
00:04:50,130 --> 00:04:52,653
regional accents are
a lot like underpants.

94
00:04:53,950 --> 00:04:59,590
Everybody has them, and usually
no one notices his or her own.

95
00:04:59,590 --> 00:05:01,950
But the world would be
a very different place

96
00:05:01,950 --> 00:05:03,710
in their absence."

97
00:05:03,710 --> 00:05:05,610
So that's what
regional accents are.

98
00:05:08,250 --> 00:05:09,770
How many of you
guys are linguists,

99
00:05:09,770 --> 00:05:10,990
or interested in linguistics?

100
00:05:12,940 --> 00:05:13,670
Just a few, OK.

101
00:05:14,870 --> 00:05:17,670
Well, of course is it's
a fascinating science,

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00:05:17,670 --> 00:05:19,650
and it intersects with
the auditory world.

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00:05:22,920 --> 00:05:26,750
So today we're going to
launch into the next aspect

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00:05:26,750 --> 00:05:29,910
of the auditory periphery
which is the inner ear.

105
00:05:29,910 --> 00:05:32,820
And the inner ear, the
scientific name, of course,

106
00:05:32,820 --> 00:05:36,820
is the cochlea, from
the Greek snail shell.

107
00:05:36,820 --> 00:05:39,600
We're going to talk about
the anatomy of the cochlea.

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00:05:39,600 --> 00:05:40,730
This is the cochlea here.

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00:05:44,110 --> 00:05:45,990
We're going to talk
about the vibration

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00:05:45,990 --> 00:05:47,620
patterns in the cochlea.

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00:05:47,620 --> 00:05:49,470
Because of course, the
cochlear structures

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00:05:49,470 --> 00:05:51,385
are vibrating in
response to sound.

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00:05:52,830 --> 00:05:56,250
And the original
pioneer in that area

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00:05:56,250 --> 00:05:58,370
was of course George
von Bekesy, who

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00:05:58,370 --> 00:06:02,290
was a Hungarian physicist
who worked for the telephone

116
00:06:02,290 --> 00:06:06,520
company, later came to
Harvard and won the Nobel

117
00:06:06,520 --> 00:06:08,690
Prize in 1961.

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00:06:08,690 --> 00:06:11,740
So we always put him
up on the pedestal

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00:06:11,740 --> 00:06:16,440
because he is the only
winner for the hearing

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00:06:16,440 --> 00:06:18,720
field for the Nobel Prize.

121
00:06:18,720 --> 00:06:21,470
So those in the
vision system, you

122
00:06:21,470 --> 00:06:24,190
can pull out all these people
who've won the Nobel Prize.

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00:06:24,190 --> 00:06:27,140
In the auditory field,
there's one winner.

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00:06:27,140 --> 00:06:28,140
It's George von Bekesy.

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00:06:28,140 --> 00:06:32,325
So we'll talk about his work
on cochlear vibration patterns.

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00:06:33,530 --> 00:06:35,990
Then we'll talk about
the receptor cells

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00:06:35,990 --> 00:06:40,160
for hearing, which are inner
hair cells and outer hair

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00:06:40,160 --> 00:06:40,660
cells.

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00:06:40,660 --> 00:06:42,120
There are two
types, a little bit

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00:06:42,120 --> 00:06:44,405
like you had the rods
and cones in the retina.

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00:06:45,890 --> 00:06:49,740
But these have very different
and complementary roles,

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00:06:49,740 --> 00:06:53,200
and we'll talk about the
separate functions of those two

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00:06:53,200 --> 00:06:54,930
types of hair cells.

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00:06:54,930 --> 00:06:57,920
We'll talk about the outer
hair cell electromotility.

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00:06:57,920 --> 00:06:59,190
We'll go into what that is.

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00:07:00,520 --> 00:07:02,060
And finally if we
have time, we'll

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00:07:02,060 --> 00:07:03,870
end up with otoacoustic
emissions, which

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00:07:03,870 --> 00:07:07,870
are a very interesting research
and clinical tool for testing

139
00:07:07,870 --> 00:07:08,370
here.

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00:07:11,280 --> 00:07:16,280
So cochlear anatomy,
here is an early drawing

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00:07:16,280 --> 00:07:20,240
of the cochlea by DeVerny.

142
00:07:20,240 --> 00:07:23,360
Back in the 1600s,
they already knew

143
00:07:23,360 --> 00:07:26,100
that the cochlea was
like a snail shell.

144
00:07:26,100 --> 00:07:28,590
And in the middle of
it, it had a membrane,

145
00:07:28,590 --> 00:07:32,570
and the membrane went all the
way from the base to the apex.

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00:07:32,570 --> 00:07:36,570
This very basalmost
part is called the hook.

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00:07:37,760 --> 00:07:42,150
And then the membrane
spirals around

148
00:07:42,150 --> 00:07:44,090
and goes to the very apex.

149
00:07:44,090 --> 00:07:48,290
And so I have a very simple
wire model that I can hold up,

150
00:07:48,290 --> 00:07:49,040
do the same thing.

151
00:07:49,040 --> 00:07:50,634
I can bend it any way I want to.

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00:07:50,634 --> 00:07:51,300
Here's the hook.

153
00:07:53,360 --> 00:07:55,240
You can see this in
three dimensions here.

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00:07:57,100 --> 00:07:59,770
OK, so the cochlea
is a spiral shaped

155
00:07:59,770 --> 00:08:02,350
structure which has
a membrane in it.

156
00:08:02,350 --> 00:08:03,850
The name of the
big membrane-- it

157
00:08:03,850 --> 00:08:06,090
has several membranes-- the
name of the big membrane

158
00:08:06,090 --> 00:08:12,000
is called the basilar
membrane, which

159
00:08:12,000 --> 00:08:13,505
of course stands for base.

160
00:08:16,910 --> 00:08:19,620
And we'll see that the hair
cells and the other cells

161
00:08:19,620 --> 00:08:23,970
associated with them sit right
on top of the basilar membrane.

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00:08:23,970 --> 00:08:26,380
We can go to that
in just a second.

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00:08:27,470 --> 00:08:31,120
Anatomists more recently
like to cut sections

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00:08:31,120 --> 00:08:32,070
through structures.

165
00:08:32,070 --> 00:08:34,600
And that's because the light
microscope, the electron

166
00:08:34,600 --> 00:08:37,960
microscope, can resolve
very small things

167
00:08:37,960 --> 00:08:43,710
like cells and parts of cells
very well in thin sections.

168
00:08:43,710 --> 00:08:47,160
So if you cut right down the
middle of that snail shell

169
00:08:47,160 --> 00:08:49,860
and took out a thin section,
you'd get this view.

170
00:08:50,920 --> 00:08:52,790
So of course, all
this gray shading

171
00:08:52,790 --> 00:08:56,380
on the outside and even
parts of the inside is bone.

172
00:08:56,380 --> 00:08:58,070
So this is a bony structure.

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00:08:58,070 --> 00:09:00,040
It's very different
from the eyeball,

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00:09:00,040 --> 00:09:01,990
which is all soft tissue.

175
00:09:01,990 --> 00:09:03,060
This is a bony structure.

176
00:09:04,180 --> 00:09:07,410
In the middle, there
is a nerve coming in.

177
00:09:07,410 --> 00:09:08,575
That's the auditory nerve.

178
00:09:09,730 --> 00:09:11,870
The auditory nerve
starts in the cochlea

179
00:09:11,870 --> 00:09:14,260
and sends messages to the
brain, which is down here.

180
00:09:14,260 --> 00:09:15,100
It's been cut away.

181
00:09:17,320 --> 00:09:23,500
You can see the tube of the
snail shell, or cochlea,

182
00:09:23,500 --> 00:09:26,460
is subdivided by this big
membrane, this basilar

183
00:09:26,460 --> 00:09:26,960
membrane.

184
00:09:26,960 --> 00:09:29,155
And that there's another
membrane in here too.

185
00:09:30,430 --> 00:09:32,704
The name of that membrane
is Reissner's membrane,

186
00:09:32,704 --> 00:09:33,870
but it's not that important.

187
00:09:35,010 --> 00:09:38,310
But the picture you
get here sort of

188
00:09:38,310 --> 00:09:40,925
looks like steps on a ladder.

189
00:09:42,380 --> 00:09:49,835
And the Latin name first steps
is "scala"-- or "scalae,"

190
00:09:49,835 --> 00:09:50,735
if it's plural.

191
00:09:51,950 --> 00:09:52,775
This means steps.

192
00:09:54,690 --> 00:09:58,160
For instance, a musical
scale is whole steps,

193
00:09:58,160 --> 00:09:59,710
and every now and
then a half step.

194
00:10:00,860 --> 00:10:02,880
So these, to the
early anatomists,

195
00:10:02,880 --> 00:10:04,940
looked like steps on a ladder.

196
00:10:04,940 --> 00:10:10,280
But actually what they are,
are fluid-filled compartments

197
00:10:10,280 --> 00:10:11,760
separated by membranes.

198
00:10:13,310 --> 00:10:17,060
And there are three
fluid-filled compartments here.

199
00:10:18,100 --> 00:10:21,060
And this is another
cross section

200
00:10:21,060 --> 00:10:23,970
of just one turn of the cochlea.

201
00:10:25,210 --> 00:10:27,680
This compartment is
called scala tympani.

202
00:10:29,269 --> 00:10:31,060
This compartment is
called scala vestibuli.

203
00:10:32,420 --> 00:10:35,320
And this one, which is in the
middle, is called scala media.

204
00:10:35,320 --> 00:10:38,185
So there are three
scalae in the cochlea.

205
00:10:39,820 --> 00:10:50,800
So scala tympani, vestibuli,
and media, or middle.

206
00:10:53,590 --> 00:10:58,550
And the hair cells
sit on this membrane

207
00:10:58,550 --> 00:11:03,930
that separates scala
tympani from scala media.

208
00:11:03,930 --> 00:11:06,110
And the hair cells here,
the inner hair cells

209
00:11:06,110 --> 00:11:08,560
and the outer hair
cells, are surrounded

210
00:11:08,560 --> 00:11:10,990
by a whole bunch of other cells.

211
00:11:10,990 --> 00:11:15,430
And that whole receptor organ
is called the organ of Corti.

212
00:11:15,430 --> 00:11:17,520
So it says that down
here, the organ of Corti.

213
00:11:17,520 --> 00:11:22,390
And Corti was one of the
first Italian anatomists

214
00:11:22,390 --> 00:11:25,400
to really draw the
structure correctly,

215
00:11:25,400 --> 00:11:27,020
although he got it
a little bit wrong.

216
00:11:27,020 --> 00:11:31,120
These round circles are
the outer hair cells.

217
00:11:31,120 --> 00:11:33,170
If you cut this in
cross section and look

218
00:11:33,170 --> 00:11:36,110
at this in a magnified
version, there's

219
00:11:36,110 --> 00:11:37,600
only one inner hair cell.

220
00:11:37,600 --> 00:11:40,665
He put two in his drawing, so
it's a little bit incorrect.

221
00:11:41,820 --> 00:11:44,360
But his name is now
attached to the organ.

222
00:11:44,360 --> 00:11:46,670
The organ of Corti is
where the hair cells are,

223
00:11:46,670 --> 00:11:49,250
and there's a whole bunch
of other supporting cells

224
00:11:49,250 --> 00:11:51,250
that keep the hair
cells in their place.

225
00:11:54,960 --> 00:11:58,745
OK, so the receptor organ
sits on the basilar membrane.

226
00:12:00,649 --> 00:12:01,940
And the organ of Corti's there.

227
00:12:01,940 --> 00:12:05,080
There's this other membrane
that separates scala media

228
00:12:05,080 --> 00:12:06,175
from scala vestibuli.

229
00:12:06,175 --> 00:12:09,110
It's called Reissner's membrane,
but it's not important.

230
00:12:09,110 --> 00:12:11,780
OK, so that's the structure
of the organ of Corti.

231
00:12:12,850 --> 00:12:16,020
And during the 1930s
and '40s, people

232
00:12:16,020 --> 00:12:18,170
started thinking about,
well, how does this thing

233
00:12:18,170 --> 00:12:21,350
move when you stimulate
the ear with sound?

234
00:12:22,930 --> 00:12:25,940
And George von Bekesy,
as I've said before,

235
00:12:25,940 --> 00:12:29,440
was the first to make
really good measurements

236
00:12:29,440 --> 00:12:32,930
of the motion of the basilar
membrane in response to sound.

237
00:12:32,930 --> 00:12:37,120
And this is a cutaway diagram
of his experimental setup.

238
00:12:37,120 --> 00:12:39,030
This is the cochlea
in cross section.

239
00:12:39,030 --> 00:12:41,280
Of course, he had the
whole cochlea there.

240
00:12:41,280 --> 00:12:44,200
And he used cochleas
from cadavers.

241
00:12:44,200 --> 00:12:48,150
He would go to the mortuary,
get a temporal bone

242
00:12:48,150 --> 00:12:50,870
and drill away all the bone
and be left with the cochlea

243
00:12:50,870 --> 00:12:52,360
and put it in his Petri dish.

244
00:12:54,170 --> 00:12:58,020
He had a huge sound
source that he

245
00:12:58,020 --> 00:13:00,610
would apply right
to the oval window.

246
00:13:00,610 --> 00:13:03,800
He would take out the stapes
and drive the cochlear fluids

247
00:13:03,800 --> 00:13:04,810
directly.

248
00:13:04,810 --> 00:13:08,434
And as we said last time,
if you have sound in air

249
00:13:08,434 --> 00:13:09,850
and are trying to
get it in fluid,

250
00:13:09,850 --> 00:13:11,370
you really to crank it up.

251
00:13:11,370 --> 00:13:14,960
And so it's a huge sound source.

252
00:13:14,960 --> 00:13:18,730
And he stimulated
way up at 140 dB,

253
00:13:18,730 --> 00:13:21,440
way at the top end of the
curve we had last time.

254
00:13:23,240 --> 00:13:25,847
He needed to drive
it that high not only

255
00:13:25,847 --> 00:13:28,860
to get sound into
the fluid but also

256
00:13:28,860 --> 00:13:32,395
so that his measurement system
could pick up these movements.

257
00:13:32,395 --> 00:13:35,130
The movements tend to
be very, very small.

258
00:13:37,310 --> 00:13:39,790
In response to sound,
maybe the basilar membrane

259
00:13:39,790 --> 00:13:42,186
is moving only a few nanometers.

260
00:13:44,260 --> 00:13:46,790
OK, but it's going to
move a lot more nanometers

261
00:13:46,790 --> 00:13:49,290
if you blast the heck out of it.

262
00:13:49,290 --> 00:13:54,610
And his observation device was
simply a microscope, a water

263
00:13:54,610 --> 00:13:57,980
immersion lens that he brought
down and focused on the basilar

264
00:13:57,980 --> 00:14:00,890
membrane to see the thing move.

265
00:14:00,890 --> 00:14:03,530
So he didn't have
very good resolution.

266
00:14:03,530 --> 00:14:06,100
Maybe he could only
see micrometers

267
00:14:06,100 --> 00:14:10,020
in terms of movements, so he
had to turn up the sound very

268
00:14:10,020 --> 00:14:11,525
high to get the
thing to vibrate.

269
00:14:13,330 --> 00:14:18,320
So we can criticize
his experiments now

270
00:14:18,320 --> 00:14:19,960
for several reasons.

271
00:14:19,960 --> 00:14:23,150
Number one, we don't
listen way up at 140 dB.

272
00:14:23,150 --> 00:14:25,080
In fact, those kinds
of sounds are actually

273
00:14:25,080 --> 00:14:26,550
damaging to the hair cells.

274
00:14:27,890 --> 00:14:31,000
But we can also say there
weren't any hair cells.

275
00:14:31,000 --> 00:14:32,225
It's a dead preparation.

276
00:14:32,225 --> 00:14:36,300
It's a cochlea
from a cadaver, OK?

277
00:14:36,300 --> 00:14:41,090
And what we know now is that
the movements and vibration

278
00:14:41,090 --> 00:14:45,520
patterns of the cochlea are very
different in a dead preparation

279
00:14:45,520 --> 00:14:47,250
than they are in a
living preparation.

280
00:14:47,250 --> 00:14:49,510
We'll get to that
in just a minute.

281
00:14:49,510 --> 00:14:52,450
In spite of those problems--
I mean, von Bekesy

282
00:14:52,450 --> 00:14:53,650
was working in the '30s.

283
00:14:53,650 --> 00:14:56,810
He didn't have very good
measurement devices,

284
00:14:56,810 --> 00:14:59,050
he had to use what he had.

285
00:14:59,050 --> 00:15:01,055
He discovered some
very important things.

286
00:15:02,290 --> 00:15:05,670
One of the things was that the
basilar membrane-- and here's

287
00:15:05,670 --> 00:15:07,780
a diagram of the
basilar membrane.

288
00:15:07,780 --> 00:15:11,120
It's this horizontal line
here, if there's no sound.

289
00:15:12,550 --> 00:15:15,960
And it's stretched out now as
if you took the snail shell

290
00:15:15,960 --> 00:15:20,930
and unwound the coil and made
it a long, straight basilar

291
00:15:20,930 --> 00:15:21,430
membrane.

292
00:15:21,430 --> 00:15:27,320
So the base is over here
and the apex is up here.

293
00:15:28,700 --> 00:15:32,500
And we think that that doesn't
change the vibration pattern

294
00:15:32,500 --> 00:15:33,590
at all.

295
00:15:33,590 --> 00:15:35,770
The only reason that
the cochlea is coiled

296
00:15:35,770 --> 00:15:37,757
is to save space in your head.

297
00:15:37,757 --> 00:15:39,215
Otherwise, it would
be pretty long.

298
00:15:40,890 --> 00:15:44,470
So unwinding this is
just a convenient way

299
00:15:44,470 --> 00:15:46,060
to look at the
vibration pattern.

300
00:15:47,370 --> 00:15:50,790
He measured in the intact
cochlea, of course.

301
00:15:51,820 --> 00:15:56,950
This pattern of vibration
that von Bekesy observed

302
00:15:56,950 --> 00:15:59,640
was called a traveling wave.

303
00:15:59,640 --> 00:16:03,310
OK, so this-- traveling
waves in the cochlea.

304
00:16:04,430 --> 00:16:08,180
And basically what that means is
these are snapshots-- one, two,

305
00:16:08,180 --> 00:16:09,490
three, and four.

306
00:16:09,490 --> 00:16:13,620
At one instant, the wave
pattern looks like number one.

307
00:16:13,620 --> 00:16:16,460
At the next instant,
it moves, or travels,

308
00:16:16,460 --> 00:16:19,880
and looks like number two,
and so on and so forth,

309
00:16:19,880 --> 00:16:21,900
three and four.

310
00:16:21,900 --> 00:16:25,230
So the traveling wave
starts in the base

311
00:16:25,230 --> 00:16:27,685
and travels up to the apex.

312
00:16:27,685 --> 00:16:31,630
And remember, the
base of the cochlear

313
00:16:31,630 --> 00:16:33,630
is where the input is coming.

314
00:16:33,630 --> 00:16:38,230
If we go back to our first
diagram here, remember,

315
00:16:38,230 --> 00:16:42,270
the stapes is pushing in
and out at the oval window.

316
00:16:42,270 --> 00:16:44,560
And that's way down at
the base of the cochlear.

317
00:16:45,620 --> 00:16:47,480
And what we're seeing
is these vibrations

318
00:16:47,480 --> 00:16:52,090
are traveling from the base
all the way up to the apex,

319
00:16:52,090 --> 00:16:54,170
and it's taking a little
bit of time to do so.

320
00:16:56,200 --> 00:16:58,790
So that's what von
Bekesy discovered--

321
00:16:58,790 --> 00:16:59,985
there's a traveling wave.

322
00:17:01,800 --> 00:17:04,690
The second thing
he discovered is

323
00:17:04,690 --> 00:17:07,990
that the peak of the traveling
wave-- you notice these dash

324
00:17:07,990 --> 00:17:13,390
curves draw the envelope or
the maximal point of movement

325
00:17:13,390 --> 00:17:15,470
of this basilar membrane.

326
00:17:15,470 --> 00:17:20,060
There's a peak of this traveling
when the basilar membrane is

327
00:17:20,060 --> 00:17:21,065
vibrating the most.

328
00:17:22,480 --> 00:17:26,470
That peak changes as a function
of the frequency of the sound

329
00:17:26,470 --> 00:17:28,415
that you used to stimulate
your preparation.

330
00:17:29,640 --> 00:17:34,610
And this diagram shows that, but
I have a little better movie,

331
00:17:34,610 --> 00:17:38,390
or demonstration, that
shows you a traveling wave

332
00:17:38,390 --> 00:17:40,590
that's a little bit
easier to understand.

333
00:17:40,590 --> 00:17:43,210
So I actually have two of them.

334
00:17:43,210 --> 00:17:45,795
These were made by Chris Shera
at Mass Eye and Ear Infirmary.

335
00:17:46,930 --> 00:17:50,550
And again, this is the
basilar membrane stretched out

336
00:17:50,550 --> 00:17:53,600
in a long line from the
base of the cochlea up

337
00:17:53,600 --> 00:17:55,400
to the apex of the cochlear.

338
00:17:55,400 --> 00:17:57,400
And this is a situation
with no sound.

339
00:17:58,500 --> 00:18:03,170
So now we're going to turn on
a sound that is a low frequency

340
00:18:03,170 --> 00:18:03,790
tone.

341
00:18:03,790 --> 00:18:09,251
So tone is synonymous with pure
tone or a single frequency.

342
00:18:09,251 --> 00:18:10,875
So it's just going
to be one frequency.

343
00:18:12,070 --> 00:18:14,990
And the input comes
in here at the stapes.

344
00:18:14,990 --> 00:18:18,170
And you'll see the pattern
of movement of the basilar

345
00:18:18,170 --> 00:18:20,680
membrane in response to
the low frequency tone.

346
00:18:20,680 --> 00:18:23,191
Whoops, pressed
the wrong button.

347
00:18:27,810 --> 00:18:30,005
It takes a little bit of
time for this to develop.

348
00:18:32,360 --> 00:18:37,200
And then you can see the complex
pattern, or traveling wave.

349
00:18:37,200 --> 00:18:40,110
It seems to start here
and go up to here.

350
00:18:40,110 --> 00:18:43,290
It goes up to a peak and
then quickly comes down.

351
00:18:43,290 --> 00:18:46,370
There's almost no movement
right at the apex there.

352
00:18:47,770 --> 00:18:53,030
So one thing about that movement
that I said before is there's

353
00:18:53,030 --> 00:18:56,940
a peak of vibration at a
certain place along the basilar

354
00:18:56,940 --> 00:18:57,810
membrane.

355
00:18:57,810 --> 00:19:00,640
The other thing is that at
any point along the basilar

356
00:19:00,640 --> 00:19:03,835
membrane that's moving, it's
moving as a function of time.

357
00:19:04,840 --> 00:19:07,750
And actually, if you knew what
the frequency of that tone

358
00:19:07,750 --> 00:19:10,670
is and looked at the
frequency of movement here,

359
00:19:10,670 --> 00:19:11,910
it would be the same.

360
00:19:11,910 --> 00:19:15,250
So the basilar membrane
is moving up and down

361
00:19:15,250 --> 00:19:18,690
at the same frequency
as the sound stimulus.

362
00:19:18,690 --> 00:19:21,170
Maybe that'll be a
little bit more clear

363
00:19:21,170 --> 00:19:24,600
when I go to the next one,
because the next movie shows

364
00:19:24,600 --> 00:19:29,330
the basilar membrane vibration
to three tones-- the low one

365
00:19:29,330 --> 00:19:32,630
that we just saw,
a middle frequency

366
00:19:32,630 --> 00:19:36,000
one, and a high frequency one.

367
00:19:36,000 --> 00:19:38,540
And as you can indicate,
you can probably

368
00:19:38,540 --> 00:19:42,100
get from my hand movements,
the low frequency tone

369
00:19:42,100 --> 00:19:47,090
is going to maximally
vibrate here toward the apex.

370
00:19:47,090 --> 00:19:51,320
The middle frequency is going
to be maximally vibrating here,

371
00:19:51,320 --> 00:19:54,900
and the high frequency is going
to be maximally vibrating over

372
00:19:54,900 --> 00:19:55,820
here.

373
00:19:55,820 --> 00:19:58,520
OK, so there's going
to sort of a frequency

374
00:19:58,520 --> 00:20:01,275
analysis along the length
of this basilar membrane.

375
00:20:02,500 --> 00:20:04,930
The other thing I want you
to notice when the movie is

376
00:20:04,930 --> 00:20:10,080
playing is how fast these
three places along the basilar

377
00:20:10,080 --> 00:20:11,860
membrane are moving,
see if they're

378
00:20:11,860 --> 00:20:14,910
moving at the same speed
or at a different speed.

379
00:20:25,300 --> 00:20:26,860
So this is the
one we had before.

380
00:20:28,280 --> 00:20:31,340
This is the middle frequency
and this is the high frequency.

381
00:20:31,340 --> 00:20:33,990
See how much faster this
is going back and forth

382
00:20:33,990 --> 00:20:36,180
than the slow one,
and see that it's

383
00:20:36,180 --> 00:20:37,490
peeking in a different place?

384
00:20:39,551 --> 00:20:40,050
OK.

385
00:20:40,050 --> 00:20:43,730
So this is, we think, due to
the physical characteristics

386
00:20:43,730 --> 00:20:46,180
of the way this
membrane is set up.

387
00:20:47,360 --> 00:20:53,430
For example, down here the
membrane is fairly tense

388
00:20:53,430 --> 00:20:56,280
and it's very short in width.

389
00:20:56,280 --> 00:21:00,010
It's like those little tiny
strings on the piano way

390
00:21:00,010 --> 00:21:02,515
up at the right end of the
piano for the high notes.

391
00:21:03,530 --> 00:21:05,865
And it's naturally going to
vibrate at high frequencies.

392
00:21:07,049 --> 00:21:08,840
When you get up toward
the apex, everything

393
00:21:08,840 --> 00:21:11,980
gets real wide in
terms of the membranes.

394
00:21:11,980 --> 00:21:13,480
The cells get bigger.

395
00:21:13,480 --> 00:21:15,920
Everything's heavier,
and it's naturally

396
00:21:15,920 --> 00:21:18,120
going to vibrate slower.

397
00:21:18,120 --> 00:21:20,560
And it's going to vibrate
best for low frequencies.

398
00:21:21,780 --> 00:21:25,250
OK, so there's this analysis
along the length of the cochlea

399
00:21:25,250 --> 00:21:28,360
in terms of high
frequencies are mapped here,

400
00:21:28,360 --> 00:21:31,264
mid frequencies are mapped
here, and low frequencies

401
00:21:31,264 --> 00:21:31,930
are mapped here.

402
00:21:31,930 --> 00:21:36,890
There is, if you will, a place
code for sound frequency.

403
00:21:44,600 --> 00:21:46,560
So sound frequencies
are broken up

404
00:21:46,560 --> 00:21:52,986
into a place code-- low
frequencies apically,

405
00:21:52,986 --> 00:21:54,735
and higher and higher
frequencies basally.

406
00:21:56,260 --> 00:22:03,040
Secondly, if you buy into
my frequency, or our timing

407
00:22:03,040 --> 00:22:12,590
of the movement, there's
also a timing code

408
00:22:12,590 --> 00:22:18,090
in that high frequencies
are vibrating much quicker

409
00:22:18,090 --> 00:22:20,245
and low frequencies are
vibrating much slower.

410
00:22:21,800 --> 00:22:23,730
And as we'll learn
in a week or two,

411
00:22:23,730 --> 00:22:27,070
the nervous system keeps
track of both of those things.

412
00:22:28,240 --> 00:22:31,340
There are hair cells down here
in the base of your cochlea

413
00:22:31,340 --> 00:22:34,950
which are connected to the
nerve fibers that only innervate

414
00:22:34,950 --> 00:22:40,030
them and are only active when
there's a high frequency sound

415
00:22:40,030 --> 00:22:41,110
stimulus.

416
00:22:41,110 --> 00:22:43,350
They send that
message to the brain.

417
00:22:43,350 --> 00:22:46,130
The brain says, ah, here
are some high frequency

418
00:22:46,130 --> 00:22:47,540
or high pitched sounds.

419
00:22:49,160 --> 00:22:52,680
Conversely, there are
hair cells up here

420
00:22:52,680 --> 00:22:55,190
that are only responding
when the basilar membrane is

421
00:22:55,190 --> 00:22:56,740
stimulated with a low frequency.

422
00:22:56,740 --> 00:23:00,990
And they're telling their
nerve fibers only send

423
00:23:00,990 --> 00:23:03,476
action potentials to the brain
when there's a low frequency

424
00:23:03,476 --> 00:23:04,100
sound stimulus.

425
00:23:05,890 --> 00:23:07,460
So what are examples?

426
00:23:07,460 --> 00:23:08,950
Everybody knows
what a low pitched

427
00:23:08,950 --> 00:23:10,116
and a high pitched sound is.

428
00:23:10,116 --> 00:23:14,080
But for example, one of the
ways you tell a male voice

429
00:23:14,080 --> 00:23:17,910
from a female voice
is that female voices

430
00:23:17,910 --> 00:23:20,520
have higher pitches to
them, higher frequencies,

431
00:23:20,520 --> 00:23:22,090
maybe an octave higher.

432
00:23:22,090 --> 00:23:25,090
So immediately usually,
even over the telephone,

433
00:23:25,090 --> 00:23:28,890
you can tell I'm talking
to a female speaker

434
00:23:28,890 --> 00:23:31,180
because the
frequencies are higher

435
00:23:31,180 --> 00:23:34,035
and they're mapped more toward
the basal end of your cochlea.

436
00:23:35,210 --> 00:23:37,900
Male voices that have
lower frequencies

437
00:23:37,900 --> 00:23:40,700
are mapped to more
apical positions.

438
00:23:40,700 --> 00:23:41,980
Any questions about that?

439
00:23:45,980 --> 00:23:50,740
Now how do we, in the modern
times, well beyond von Bekesy,

440
00:23:50,740 --> 00:23:52,820
how do we measure these motions?

441
00:23:52,820 --> 00:23:56,390
You're sort of taking
it for granted from me

442
00:23:56,390 --> 00:23:58,200
that we can make
these measurements.

443
00:23:58,200 --> 00:24:01,490
Well, von Bekesy used an
ordinary light microscope.

444
00:24:01,490 --> 00:24:05,110
And he really had to
crank things way up

445
00:24:05,110 --> 00:24:08,390
to see the structures moving.

446
00:24:08,390 --> 00:24:11,470
And we want to measure them
down near where we usually

447
00:24:11,470 --> 00:24:15,155
hear, 20 dB SPL, 40 dB SPL.

448
00:24:16,710 --> 00:24:22,930
So what's used is, on
to the basilar membrane,

449
00:24:22,930 --> 00:24:24,385
you put some sort of source.

450
00:24:25,950 --> 00:24:30,010
And maybe in the
1980s and '90s, people

451
00:24:30,010 --> 00:24:33,906
were using radioactive sources
and using the Mossbauer

452
00:24:33,906 --> 00:24:34,405
technique.

453
00:24:35,520 --> 00:24:39,320
They knew that the radioactive
particles being emitted

454
00:24:39,320 --> 00:24:42,880
had a certain frequency, and
when the basilar membrane

455
00:24:42,880 --> 00:24:44,960
was moving toward
you, the frequency

456
00:24:44,960 --> 00:24:48,530
would be changed versus
moving away from you.

457
00:24:48,530 --> 00:24:52,440
Nowadays in the '90s
and 200s, people

458
00:24:52,440 --> 00:24:56,580
are using spots
that they put down,

459
00:24:56,580 --> 00:24:59,190
like little reflective
disks that are put down

460
00:24:59,190 --> 00:25:02,030
onto the basilar membrane
that reflect light.

461
00:25:02,030 --> 00:25:05,850
And you shine down a light
onto the basilar membrane.

462
00:25:05,850 --> 00:25:09,350
And that spot reflects
the light back to you.

463
00:25:09,350 --> 00:25:11,300
You can compare the
light you sent down

464
00:25:11,300 --> 00:25:13,770
with the light that's
reflected back.

465
00:25:13,770 --> 00:25:17,320
If the membrane is
moving away from you,

466
00:25:17,320 --> 00:25:21,430
that light will be
shifted to a higher

467
00:25:21,430 --> 00:25:24,880
wavelength versus if
it's coming toward you,

468
00:25:24,880 --> 00:25:26,690
it'll be a lower wavelength.

469
00:25:26,690 --> 00:25:29,195
And this process is
called interferometry.

470
00:25:37,130 --> 00:25:41,310
And if the source is moving like
the basilar membrane is moving

471
00:25:41,310 --> 00:25:43,390
when you stimulate
it with sound,

472
00:25:43,390 --> 00:25:47,210
you can use a laser
to shine the light,

473
00:25:47,210 --> 00:25:52,570
and you can use the Doppler
interferometer-- which

474
00:25:52,570 --> 00:25:59,270
is a device that measures the
shift in light when there's

475
00:25:59,270 --> 00:26:02,570
a moving light source or
a moving light reflection.

476
00:26:02,570 --> 00:26:07,070
You can calibrate this in
terms of the displacement

477
00:26:07,070 --> 00:26:12,850
or the velocity that the object
doing the reflecting is giving.

478
00:26:12,850 --> 00:26:14,330
It's shifting the
light, basically.

479
00:26:15,770 --> 00:26:20,417
So that's how most modern
experiment experiments measure

480
00:26:20,417 --> 00:26:22,500
of the movement of structures,
even though they're

481
00:26:22,500 --> 00:26:25,510
very, very small movements,
like in terms of nanometers.

482
00:26:26,960 --> 00:26:33,000
So let's see what this-- these
are data from the 1980s using

483
00:26:33,000 --> 00:26:35,665
a Mossbauer technique,
a radioactive source.

484
00:26:35,665 --> 00:26:38,480
So instead of
reflecting light, you're

485
00:26:38,480 --> 00:26:41,460
measuring the emitted
wavelengths of particles

486
00:26:41,460 --> 00:26:45,745
from a radioactive source at one
point on the basilar membrane.

487
00:26:47,030 --> 00:26:49,160
And you're stimulating
the basilar membrane

488
00:26:49,160 --> 00:26:51,180
with sound of
different frequencies,

489
00:26:51,180 --> 00:26:53,560
and you're measuring
how much it moves

490
00:26:53,560 --> 00:26:55,310
in terms of the
basilar membrane.

491
00:26:56,222 --> 00:26:57,513
I think this says displacement.

492
00:26:59,266 --> 00:27:00,275
Is that what it says?

493
00:27:00,275 --> 00:27:02,030
It says amplitude in dB.

494
00:27:03,530 --> 00:27:07,060
This is a displacement
scale, how much movement

495
00:27:07,060 --> 00:27:10,780
you're getting, as a
function of sound frequency

496
00:27:10,780 --> 00:27:14,380
for one particular point
on the basilar membrane.

497
00:27:16,570 --> 00:27:18,600
So you change your
sound frequency.

498
00:27:18,600 --> 00:27:20,900
Start with low
frequencies at 20 dB.

499
00:27:20,900 --> 00:27:23,220
Pretty low level sound.

500
00:27:23,220 --> 00:27:24,655
You don't find
much displacement.

501
00:27:26,110 --> 00:27:30,410
Go up to 6 kilohertz, find
a little bit more movement.

502
00:27:31,640 --> 00:27:34,180
Go up to 10 kilohertz,
it's getting bigger.

503
00:27:34,180 --> 00:27:36,670
And then all of a sudden
at about 16 kilohertz,

504
00:27:36,670 --> 00:27:38,810
you get a huge
amount of movement.

505
00:27:38,810 --> 00:27:40,960
You're right at the peak
of the traveling wave.

506
00:27:42,200 --> 00:27:45,780
Go up to 18 kilohertz and
it goes way back down again.

507
00:27:45,780 --> 00:27:48,040
And 20 kilohertz
there's no point

508
00:27:48,040 --> 00:27:51,320
plotted because you can't
get the thing to move at all.

509
00:27:52,490 --> 00:27:55,780
It's a very
sharply-tuned function

510
00:27:55,780 --> 00:27:58,600
of movement in terms of
the sound frequencies.

511
00:27:58,600 --> 00:28:02,720
This place is only
moving-- or mostly

512
00:28:02,720 --> 00:28:07,160
moving-- for a sound
frequency of 16 kilohertz

513
00:28:07,160 --> 00:28:08,890
in terms of where
the source was.

514
00:28:11,110 --> 00:28:15,970
Change the sound level to
40 or 60 or even 80 dB--

515
00:28:15,970 --> 00:28:19,200
80 dB is a sound
that is certainly

516
00:28:19,200 --> 00:28:21,510
within conversational speech.

517
00:28:21,510 --> 00:28:25,345
It's a high level sound, but
it's not painful or damaging

518
00:28:25,345 --> 00:28:26,080
at all.

519
00:28:27,460 --> 00:28:29,476
In that case, the
function is much broader.

520
00:28:31,410 --> 00:28:34,030
If you just looked at
that function, you'd say,

521
00:28:34,030 --> 00:28:36,650
well, this point on the
basilar membrane years

522
00:28:36,650 --> 00:28:38,565
is responding to many
sound frequencies.

523
00:28:39,770 --> 00:28:42,100
It's not responding
to 20 kilohertz,

524
00:28:42,100 --> 00:28:44,380
but it's responding to
everything below that.

525
00:28:45,670 --> 00:28:48,850
And if you were to-- they
didn't here because they wanted

526
00:28:48,850 --> 00:28:50,310
to take care of
their preparation

527
00:28:50,310 --> 00:28:53,010
and not damage it-- if
they want up to the levels

528
00:28:53,010 --> 00:28:57,825
that von Bekesy used, 140 dB,
it would be completely flat.

529
00:28:59,210 --> 00:29:03,050
And von Bekesy found that the
tuning of the basilar membrane

530
00:29:03,050 --> 00:29:06,140
was very flat, or
just broadly tuned.

531
00:29:07,160 --> 00:29:13,360
But these modern measurements
show extremely sharp functions

532
00:29:13,360 --> 00:29:16,340
for a single point of movement
on the basilar membrane.

533
00:29:20,190 --> 00:29:25,845
This is a plot of the same
data, but plotted a little bit

534
00:29:25,845 --> 00:29:26,345
differently.

535
00:29:27,630 --> 00:29:29,610
This axis is still
sound frequency.

536
00:29:31,060 --> 00:29:34,640
And now we're going to
plot it on the x-axis.

537
00:29:34,640 --> 00:29:37,410
It's still a dB scale,
but now on the y-axis

538
00:29:37,410 --> 00:29:41,040
it's threshold dB SPL.

539
00:29:41,040 --> 00:29:42,390
So what's threshold?

540
00:29:42,390 --> 00:29:45,290
Well in this case, it
doesn't really make sense.

541
00:29:45,290 --> 00:29:50,110
I think it would've been better
to label this some criterion

542
00:29:50,110 --> 00:29:53,940
displacement, because the
criterion displacement

543
00:29:53,940 --> 00:29:59,740
use for this lowest
curve is 0.35 nanometers.

544
00:29:59,740 --> 00:30:02,530
And what the experiment now,
or what the plotting now

545
00:30:02,530 --> 00:30:10,640
is how much sound level do we
have to crank into the system

546
00:30:10,640 --> 00:30:13,630
to get this point on
the basilar membrane

547
00:30:13,630 --> 00:30:18,030
to vibrate 0.35 nanometers?

548
00:30:18,030 --> 00:30:22,360
OK, in the case of 16
kilohertz right here,

549
00:30:22,360 --> 00:30:26,000
at the lowest point, we
only had to put in 10 dB,

550
00:30:26,000 --> 00:30:27,490
not very much sound at all.

551
00:30:29,000 --> 00:30:31,660
At 14 kilohertz,
at 19 kilohertz,

552
00:30:31,660 --> 00:30:33,970
we had to turn the
sound up a little bit.

553
00:30:35,920 --> 00:30:39,730
At 20 kilohertz, we turned
up the sound so much,

554
00:30:39,730 --> 00:30:43,800
but we said could never get
it to vibrate 0.35 nanometers.

555
00:30:43,800 --> 00:30:45,370
So there's no point
plotted there.

556
00:30:46,450 --> 00:30:51,010
At 5 kilohertz, we had to crank
up the sound to about 60 dB

557
00:30:51,010 --> 00:30:56,250
to get this point to
vibrate 0.35 nanometers.

558
00:30:56,250 --> 00:30:58,300
So you're asking for
the point to give you

559
00:30:58,300 --> 00:31:01,690
some specified
amount of vibration

560
00:31:01,690 --> 00:31:04,220
or a criterion of vibration.

561
00:31:04,220 --> 00:31:06,150
And you're plotting
this function here.

562
00:31:07,240 --> 00:31:10,950
And this is a very
important curve.

563
00:31:10,950 --> 00:31:14,400
We'll be seeing this many, many
times the rest of the semester.

564
00:31:16,352 --> 00:31:18,480
And it's called a tuning curve.

565
00:31:26,680 --> 00:31:28,620
So you should all
be familiar with how

566
00:31:28,620 --> 00:31:31,870
this tuning curve is generated.

567
00:31:31,870 --> 00:31:35,585
You can make a tuning curve for
a recording from a hair cell.

568
00:31:37,140 --> 00:31:38,940
You could make a tuning
curve for recording

569
00:31:38,940 --> 00:31:40,890
from a nerve fiber.

570
00:31:40,890 --> 00:31:44,330
Let's say we put on an
electrode in the auditory nerve.

571
00:31:44,330 --> 00:31:46,970
You guys have talked
about this term,

572
00:31:46,970 --> 00:31:49,600
this technique called
single unit recording

573
00:31:49,600 --> 00:31:51,750
where you put an
electrode in a nerve--

574
00:31:51,750 --> 00:31:55,630
say, the optic nerve-- and
you measure the spikes coming

575
00:31:55,630 --> 00:31:59,280
from the single axon that
you're recording from.

576
00:31:59,280 --> 00:32:00,920
And you might say,
well, I'm going

577
00:32:00,920 --> 00:32:06,417
to turn the sound up until
I get 10 spikes per second.

578
00:32:06,417 --> 00:32:07,250
That's my criterion.

579
00:32:08,400 --> 00:32:10,590
And I'm going to
change the frequency.

580
00:32:10,590 --> 00:32:16,390
How much sound level do I
have to stimulate the ear with

581
00:32:16,390 --> 00:32:21,140
to get the auditory nerve fiber
to fire 10 spikes per second?

582
00:32:21,140 --> 00:32:25,860
Well, at 16 kilohertz I have to
hardly put any sound in at all.

583
00:32:25,860 --> 00:32:29,620
But 2 kilohertz, I have
to really blast the thing.

584
00:32:29,620 --> 00:32:32,960
So this auditory nerve
fiber is very tuned

585
00:32:32,960 --> 00:32:34,190
to the sound frequency.

586
00:32:34,190 --> 00:32:39,330
It's sharply tuned, OK, to a
frequency near 16 kilohertz.

587
00:32:40,810 --> 00:32:44,000
You could make a tuning
curve from a receptor cell

588
00:32:44,000 --> 00:32:49,640
by saying how much receptor
potential do I want?

589
00:32:49,640 --> 00:32:53,310
Let's say one microvolt of
response or receptor potential

590
00:32:53,310 --> 00:32:54,940
from the hair cell.

591
00:32:54,940 --> 00:32:57,110
What sort of sound
level do I need

592
00:32:57,110 --> 00:32:59,800
to dial into the ear at
these different frequencies

593
00:32:59,800 --> 00:33:02,315
to get that criterion
receptor potential?

594
00:33:02,315 --> 00:33:03,100
Is that clear?

595
00:33:04,350 --> 00:33:08,242
So these tuning
curves are omnipresent

596
00:33:08,242 --> 00:33:09,575
throughout the auditory pathway.

597
00:33:10,740 --> 00:33:12,930
And they're a measure of
the sharpness of tuning.

598
00:33:12,930 --> 00:33:17,560
They're a measure of whether one
place on the basilar membrane

599
00:33:17,560 --> 00:33:21,530
or one auditory nerve fiber
can listen to 16 kilohertz

600
00:33:21,530 --> 00:33:24,240
and ignore 20 kilohertz.

601
00:33:24,240 --> 00:33:25,940
It's very important
if you're trying

602
00:33:25,940 --> 00:33:29,160
to know in the
pattern of harmonics

603
00:33:29,160 --> 00:33:31,050
that harmonic number
two is missing,

604
00:33:31,050 --> 00:33:34,930
you better listen to
number two with a very

605
00:33:34,930 --> 00:33:37,015
sensitive and
sharply-tuned function.

606
00:33:38,040 --> 00:33:40,480
And you have that in
the auditory system

607
00:33:40,480 --> 00:33:43,290
starting with the vibration
of the basilar membrane.

608
00:33:49,420 --> 00:33:51,580
What are these receptor
cells for hearing?

609
00:33:51,580 --> 00:33:55,820
So the receptor cells for
hearing are called hair cells.

610
00:33:55,820 --> 00:33:58,239
That's kind of a
funny name, right?

611
00:33:58,239 --> 00:33:59,780
But they get their
name from the fact

612
00:33:59,780 --> 00:34:03,520
that they have hairs coming
out the top of them-- at least,

613
00:34:03,520 --> 00:34:05,520
it looked that way to the
early neuroanatomists.

614
00:34:09,730 --> 00:34:14,274
So these hairs are more
properly called stereocilia.

615
00:34:17,580 --> 00:34:19,775
And let me write that
down here, stereocilia.

616
00:34:26,100 --> 00:34:31,590
And even that more proper
term is kind of a misnomer,

617
00:34:31,590 --> 00:34:42,920
because it has as
part of it "cilium."

618
00:34:42,920 --> 00:34:44,969
That's really a misnomer.

619
00:34:44,969 --> 00:34:46,530
What is a cilium on a cell?

620
00:34:46,530 --> 00:34:47,690
Does anybody know?

621
00:34:49,799 --> 00:34:50,715
AUDIENCE: [INAUDIBLE].

622
00:34:55,484 --> 00:34:56,150
PROFESSOR: Yeah.

623
00:34:56,150 --> 00:35:00,620
And they can propel single
cells through a medium, right?

624
00:35:00,620 --> 00:35:04,860
And they're wavy and floppy,
and if you look at them

625
00:35:04,860 --> 00:35:08,600
in cross-section of the
electron microscope,

626
00:35:08,600 --> 00:35:15,885
they have these sort of 9
plus 2 tubular arrangements.

627
00:35:17,470 --> 00:35:20,850
The stereociliae do not
look like that at all.

628
00:35:20,850 --> 00:35:28,020
They should be called
stereomicrovilli,

629
00:35:28,020 --> 00:35:30,470
because when you look
at them in cross section

630
00:35:30,470 --> 00:35:32,270
you see all these
filaments but there's

631
00:35:32,270 --> 00:35:34,010
no organization to them.

632
00:35:36,240 --> 00:35:39,390
And you can see the
filaments right here

633
00:35:39,390 --> 00:35:44,190
in longitudinal section going
up into the stereocilia.

634
00:35:46,590 --> 00:35:49,880
And these keep the
stereocilia very stiff.

635
00:35:51,900 --> 00:35:56,070
So when sound comes and
moves a stereocilium,

636
00:35:56,070 --> 00:35:58,780
it's sort of like a telephone
pole in a hurricane.

637
00:35:58,780 --> 00:36:02,185
It pivots around its base,
but it doesn't flop around.

638
00:36:03,686 --> 00:36:05,060
And the base of
these stereocilia

639
00:36:05,060 --> 00:36:09,610
are right as they insert
part of the cell right.

640
00:36:09,610 --> 00:36:11,325
They're very stiff structures.

641
00:36:13,330 --> 00:36:18,710
Furthermore, they're all
attached one to another.

642
00:36:18,710 --> 00:36:22,980
So all the stereocilia
on a hair cell

643
00:36:22,980 --> 00:36:27,240
tend to move together back and
forth in response to sound.

644
00:36:28,650 --> 00:36:30,830
And especially, they're
attached, of course,

645
00:36:30,830 --> 00:36:33,150
at the base, but
they're also attached

646
00:36:33,150 --> 00:36:37,380
at the very tips in
something called tip links.

647
00:36:37,380 --> 00:36:40,470
And I think I have a
picture or a diagram.

648
00:36:40,470 --> 00:36:46,820
So here are some tip links that
connects the very tallest part

649
00:36:46,820 --> 00:36:52,225
of one stereocilium to its next
tallest neighbor stereocilium.

650
00:36:53,800 --> 00:36:57,420
So the whole bundle
of stereocilia

651
00:36:57,420 --> 00:37:01,780
move together in a
rigid, pivoting way.

652
00:37:01,780 --> 00:37:07,000
And the whole bundle
is usually called just

653
00:37:07,000 --> 00:37:14,860
in jargon terms,
the "hair bundle"

654
00:37:14,860 --> 00:37:17,160
at the top of a hair cell.

655
00:37:17,160 --> 00:37:19,250
And I have some numbers for you.

656
00:37:19,250 --> 00:37:24,030
How many stereocilia are there
in the hair bundle of a given

657
00:37:24,030 --> 00:37:24,650
cell?

658
00:37:24,650 --> 00:37:38,030
So there are 40 stereocilia
for one inner hair cell.

659
00:37:38,030 --> 00:37:39,680
We haven't talked
about what these are,

660
00:37:39,680 --> 00:37:41,510
but these are in your cochlea.

661
00:37:41,510 --> 00:37:43,580
They have inner hair cells
and outer hair cells.

662
00:37:46,450 --> 00:37:56,080
And there are about
140 stereocilia

663
00:37:56,080 --> 00:37:59,600
in the hair bundle of a
given outer hair cell.

664
00:37:59,600 --> 00:38:04,015
OK, there are many
stereocilia per cell.

665
00:38:05,600 --> 00:38:09,050
In this cross section, you're
just seeing three rows,

666
00:38:09,050 --> 00:38:12,060
but there are many per row.

667
00:38:12,060 --> 00:38:14,750
And here's a whole big
hair bundle all together.

668
00:38:14,750 --> 00:38:16,830
Now, why are these
exact numbers important?

669
00:38:16,830 --> 00:38:21,430
Well, it isn't that
important, except we

670
00:38:21,430 --> 00:38:27,950
think that the channel that
opens up when this hair

671
00:38:27,950 --> 00:38:30,460
bundle moves in
response to sound

672
00:38:30,460 --> 00:38:34,530
is located right at the
tips of the stereocilia.

673
00:38:34,530 --> 00:38:36,760
And most people
believe that there

674
00:38:36,760 --> 00:38:42,630
is one channel at the tip
of each stereocilium which

675
00:38:42,630 --> 00:38:49,280
would suggest that each outer
hair cell has 140 channels

676
00:38:49,280 --> 00:38:51,520
and each inner hair
cell has 40 channels.

677
00:38:51,520 --> 00:38:52,990
Now, what are these channels?

678
00:38:52,990 --> 00:38:58,260
Sometimes they're called
the transduction channels.

679
00:39:04,410 --> 00:39:06,200
What's transduction?

680
00:39:06,200 --> 00:39:06,820
Anybody?

681
00:39:06,820 --> 00:39:09,595
What's a transducer
in engineering terms?

682
00:39:13,730 --> 00:39:15,180
Anybody?

683
00:39:15,180 --> 00:39:17,026
What does it mean to
transduce something?

684
00:39:18,750 --> 00:39:20,044
Well, you can have-- yeah?

685
00:39:20,044 --> 00:39:20,960
AUDIENCE: [INAUDIBLE]?

686
00:39:22,720 --> 00:39:23,890
PROFESSOR: Exactly right.

687
00:39:23,890 --> 00:39:28,460
So you can have an accelerometer
which converts acceleration

688
00:39:28,460 --> 00:39:30,260
to an electrical signal.

689
00:39:30,260 --> 00:39:34,710
In this case, the
physical energy of sound

690
00:39:34,710 --> 00:39:35,960
is mechanical energy.

691
00:39:35,960 --> 00:39:38,850
It's movement, movement
of the tympanic membrane,

692
00:39:38,850 --> 00:39:41,350
movement of the ossicles,
movement of the basilar

693
00:39:41,350 --> 00:39:43,090
membrane up and down.

694
00:39:43,090 --> 00:39:46,030
These cells are sitting
on the basilar membrane.

695
00:39:46,030 --> 00:39:48,660
And the hair bundle is
moving back and forth.

696
00:39:50,020 --> 00:39:52,580
But the code of the
nervous system--

697
00:39:52,580 --> 00:39:54,810
we've been talking
about spikes--

698
00:39:54,810 --> 00:39:57,560
somehow you have to get
that mechanical energy

699
00:39:57,560 --> 00:40:02,320
into the electrical energy
of, in the case of hair cells,

700
00:40:02,320 --> 00:40:06,260
the receptor potentials, and in
the case of the nerve fibers,

701
00:40:06,260 --> 00:40:07,920
the action potentials
that are going

702
00:40:07,920 --> 00:40:10,310
to send messages to the brain.

703
00:40:10,310 --> 00:40:13,230
So the transduction
channel is the channel

704
00:40:13,230 --> 00:40:16,570
that responds to
mechanical energy

705
00:40:16,570 --> 00:40:21,100
and allows ions to
flow into the hair

706
00:40:21,100 --> 00:40:23,650
cell-- that is, it opens up.

707
00:40:24,680 --> 00:40:27,040
And in the case of these
transduction channels,

708
00:40:27,040 --> 00:40:34,140
it allows positive
ions, mostly potassium

709
00:40:34,140 --> 00:40:37,240
because there is a high
concentration of potassium

710
00:40:37,240 --> 00:40:39,810
in the fluid of scala media.

711
00:40:39,810 --> 00:40:41,460
Remember, these
cells are sitting in

712
00:40:41,460 --> 00:40:44,130
between scala tympani
and scala media.

713
00:40:44,130 --> 00:40:45,565
So scala media is up here.

714
00:40:46,790 --> 00:40:48,520
The transduction channel opens.

715
00:40:48,520 --> 00:40:50,360
And it's relatively
non-selective,

716
00:40:50,360 --> 00:40:55,840
but the big positive-- it's
non-selected for positive ions

717
00:40:55,840 --> 00:40:56,750
or cations.

718
00:40:56,750 --> 00:40:59,040
The big concentration
here is potassium,

719
00:40:59,040 --> 00:41:04,640
so potassium is probably the ion
that flows into the hair cells

720
00:41:04,640 --> 00:41:07,360
when the transduction
channels open up.

721
00:41:09,650 --> 00:41:13,200
And the evidence for that here
is in part from Hudspeth's lab.

722
00:41:14,470 --> 00:41:18,430
He probed around the hair
cells while the hair bundle

723
00:41:18,430 --> 00:41:21,000
was moved back and forth.

724
00:41:21,000 --> 00:41:25,370
And he found big
potentials up near the tips

725
00:41:25,370 --> 00:41:28,650
of the stereocilia and
very small potentials

726
00:41:28,650 --> 00:41:30,560
in the rest of the cell.

727
00:41:30,560 --> 00:41:33,710
So there's very good evidence
that the transduction channels

728
00:41:33,710 --> 00:41:35,820
are at the tips
of the hair cells.

729
00:41:35,820 --> 00:41:39,040
We don't know what the
transduction channels are.

730
00:41:39,040 --> 00:41:40,930
People are actively
working on that.

731
00:41:42,490 --> 00:41:45,040
So there's a guy at
Harvard in the Department

732
00:41:45,040 --> 00:41:49,750
of Neurobiology, Jeff Holt,
who thinks the transduction

733
00:41:49,750 --> 00:41:55,690
channel, this so-called
transmembrane channel, TMC,

734
00:41:55,690 --> 00:41:58,290
of which there are two
varieties, 1 and 2.

735
00:42:00,630 --> 00:42:02,680
It's not clear if
that's actually

736
00:42:02,680 --> 00:42:05,840
the channel or something
associated with the channel.

737
00:42:05,840 --> 00:42:08,290
But when you knock it
out, the hair cells

738
00:42:08,290 --> 00:42:09,550
don't respond anymore.

739
00:42:09,550 --> 00:42:10,415
The animal is deaf.

740
00:42:12,090 --> 00:42:16,460
OK, so these
transmembrane channels

741
00:42:16,460 --> 00:42:19,610
may be the transduction channel,
but the jury is still out.

742
00:42:25,280 --> 00:42:30,910
OK, so let me go back to
our generic hair cell.

743
00:42:30,910 --> 00:42:33,890
We've talked about
the stereocilia

744
00:42:33,890 --> 00:42:34,910
here and their movement.

745
00:42:34,910 --> 00:42:38,910
That's the input end
of the hair cell.

746
00:42:38,910 --> 00:42:41,725
The middle part of the
hair cell has a nucleus.

747
00:42:44,230 --> 00:42:45,410
It has a membrane.

748
00:42:45,410 --> 00:42:47,120
It has mitochondria.

749
00:42:47,120 --> 00:42:49,400
And down here, you
might think of this part

750
00:42:49,400 --> 00:42:51,490
as the output end
of the hair cell.

751
00:42:51,490 --> 00:42:55,370
This is where the hair cell
is giving its information

752
00:42:55,370 --> 00:42:57,090
to the associated nerve fibers.

753
00:42:58,660 --> 00:43:03,580
And there are, interestingly,
two types of nerve fibers.

754
00:43:03,580 --> 00:43:05,720
The one you would
instantly think of

755
00:43:05,720 --> 00:43:11,090
is the afferent nerve fiber,
the auditory nerve fiber,

756
00:43:11,090 --> 00:43:16,060
where the hair cell is sending
messages to the nerve fiber.

757
00:43:16,060 --> 00:43:19,060
And how does one
cell send a message

758
00:43:19,060 --> 00:43:21,050
to another in the
nervous system?

759
00:43:21,050 --> 00:43:22,790
Well, there's a synapse, right?

760
00:43:25,300 --> 00:43:32,345
So there's a hair cell
to nerve fiber synapse.

761
00:43:41,020 --> 00:43:42,600
And that's right here.

762
00:43:42,600 --> 00:43:47,300
And this hair cell then
releases transmitter,

763
00:43:47,300 --> 00:43:48,865
because this is a
chemical synapse.

764
00:43:54,730 --> 00:43:56,720
And it uses a neurotransmitter.

765
00:43:56,720 --> 00:43:59,910
Right, everybody knows
what neurotransmitters are.

766
00:43:59,910 --> 00:44:02,316
The neurotransmitter here
is probably glutamate.

767
00:44:06,970 --> 00:44:09,075
And so that's an excitatory
neurotransmitter.

768
00:44:23,650 --> 00:44:25,865
OK, so the hair cell then
releases the glutamate.

769
00:44:25,865 --> 00:44:28,690
It goes through
the synaptic cleft.

770
00:44:28,690 --> 00:44:31,220
There's a glutamate
receptor that it binds to

771
00:44:31,220 --> 00:44:33,390
on the auditory nerve fiber.

772
00:44:33,390 --> 00:44:36,025
The auditory nerve fiber
is depolarized or excited.

773
00:44:37,190 --> 00:44:39,010
It starts to fire
action potentials.

774
00:44:39,010 --> 00:44:40,718
And then these action
potentials are then

775
00:44:40,718 --> 00:44:43,254
sent down the auditory
nerve and into the brain.

776
00:44:43,254 --> 00:44:44,795
The brain says, aha,
there's a sound.

777
00:44:48,200 --> 00:44:50,400
Now interestingly,
there's another kind

778
00:44:50,400 --> 00:44:53,490
of nerve fiber associated
with many hair cells,

779
00:44:53,490 --> 00:44:57,260
and it's called an
efferent nerve fiber.

780
00:44:57,260 --> 00:45:02,000
So what's the difference between
an afferent and an efferent?

781
00:45:02,880 --> 00:45:03,380
anybody?

782
00:45:05,929 --> 00:45:07,470
AUDIENCE: Directionality
of the cell?

783
00:45:07,470 --> 00:45:08,540
PROFESSOR: That's right.

784
00:45:08,540 --> 00:45:10,080
So, which one goes which way.

785
00:45:10,080 --> 00:45:13,430
We've said this one is going--
the afferent is going that way.

786
00:45:14,900 --> 00:45:17,280
The efferent nerve ending
is going the opposite way.

787
00:45:17,280 --> 00:45:22,480
And so most of this
naming nomenclature

788
00:45:22,480 --> 00:45:25,810
comes from the reference
being the brain.

789
00:45:27,070 --> 00:45:29,880
The brain is where
the action is, right?

790
00:45:29,880 --> 00:45:31,960
The cochlea's way out here.

791
00:45:31,960 --> 00:45:34,880
So anything that's
going out from the brain

792
00:45:34,880 --> 00:45:38,540
is efflux or
efferent, so signals

793
00:45:38,540 --> 00:45:42,150
that are going from the brain
out to peripheral structures--

794
00:45:42,150 --> 00:45:46,670
like the hair cells-- travel by
way of efferent nerve fibers,

795
00:45:46,670 --> 00:45:47,170
right?

796
00:45:47,170 --> 00:45:49,190
Another efferent
type of nerve fiber

797
00:45:49,190 --> 00:45:52,840
would be a motor neuron, a
motor neuron sending messages

798
00:45:52,840 --> 00:45:54,340
from the brain out
to the periphery

799
00:45:54,340 --> 00:45:55,960
to contract the muscles.

800
00:45:55,960 --> 00:45:59,450
That'd be another type
of efferent nerve fiber.

801
00:45:59,450 --> 00:46:03,970
So interestingly, the hair
cells have efferent nerve fibers

802
00:46:03,970 --> 00:46:07,670
attached to them, and they form
synapses on the hair cells.

803
00:46:07,670 --> 00:46:11,580
And you do not see this
in the visual system.

804
00:46:11,580 --> 00:46:15,020
You do not see efferent
innervation of the receptor

805
00:46:15,020 --> 00:46:20,480
cells or of the retina at
all in vision, at least

806
00:46:20,480 --> 00:46:22,220
in mammalian systems.

807
00:46:22,220 --> 00:46:24,830
You do see it in
lower vertebrates.

808
00:46:26,060 --> 00:46:30,259
But in mammalian systems,
the auditory hair cells

809
00:46:30,259 --> 00:46:31,425
get an efferent innervation.

810
00:46:32,950 --> 00:46:35,200
There are hair cells as
another part of the inner ear.

811
00:46:35,200 --> 00:46:37,650
We talked about the
vestibular system

812
00:46:37,650 --> 00:46:39,015
and the semicircular canals.

813
00:46:40,250 --> 00:46:45,740
That is a hair cell organ,
and those get efferent nerve

814
00:46:45,740 --> 00:46:46,950
endings from the brain.

815
00:46:48,290 --> 00:46:54,240
And in the sides of the
body in amphibians and fish,

816
00:46:54,240 --> 00:46:57,070
there's a lateral line
system of hair cells

817
00:46:57,070 --> 00:47:01,285
that allows the fish to detect
currents of motion of water.

818
00:47:02,420 --> 00:47:05,460
And those are hair
cell-based receptor organs,

819
00:47:05,460 --> 00:47:09,570
and they get an efferent as
well as an afferent innervation.

820
00:47:09,570 --> 00:47:13,570
So it seems like wherever there
are hair cell-based systems,

821
00:47:13,570 --> 00:47:16,510
the brain sends messages
out to the hair cells

822
00:47:16,510 --> 00:47:18,820
as well as getting information
from the hair cells.

823
00:47:18,820 --> 00:47:22,510
So we'll have a
lecture later on what

824
00:47:22,510 --> 00:47:24,300
these efferent nerves are doing.

825
00:47:24,300 --> 00:47:26,900
I mean, why would the
brain want to control

826
00:47:26,900 --> 00:47:28,020
the auditory periphery?

827
00:47:29,110 --> 00:47:31,110
It's an interesting
question, and maybe there

828
00:47:31,110 --> 00:47:32,920
are several answers to that.

829
00:47:32,920 --> 00:47:34,850
Certainly, the
brain wants to know

830
00:47:34,850 --> 00:47:36,900
what's happening
to the hair cells.

831
00:47:36,900 --> 00:47:42,120
So these afferent nerve
fibers are sending messages

832
00:47:42,120 --> 00:47:43,710
when the hair cell
is stimulated.

833
00:47:43,710 --> 00:47:45,820
So that's the main pathway
going into the brain.

834
00:47:51,570 --> 00:48:00,295
OK, we've talked about
the transduction channels.

835
00:48:01,670 --> 00:48:05,110
We haven't talked about these
little things called tip links.

836
00:48:06,510 --> 00:48:09,980
One idea is that these
links between the tips

837
00:48:09,980 --> 00:48:15,410
of the stereocilia are sort
of like a rope on a trap door.

838
00:48:15,410 --> 00:48:18,590
And when the stereocilium moves,
it opens up the trap door,

839
00:48:18,590 --> 00:48:21,150
and that's what opens
the ion channel.

840
00:48:21,150 --> 00:48:22,750
These little tip
links are something

841
00:48:22,750 --> 00:48:24,560
you see in the
electron microscope.

842
00:48:24,560 --> 00:48:26,580
They're very, very fine.

843
00:48:26,580 --> 00:48:30,340
When you use some chemical
treatment to dissolve those tip

844
00:48:30,340 --> 00:48:33,790
links, the hair cells
don't work anymore.

845
00:48:33,790 --> 00:48:35,550
They don't respond
to sound anymore.

846
00:48:35,550 --> 00:48:38,290
So there are some
other proteins up

847
00:48:38,290 --> 00:48:41,011
there associated with the
transduction channels called

848
00:48:41,011 --> 00:48:41,510
tip links.

849
00:48:43,380 --> 00:48:46,772
That's a very active
area of research now--

850
00:48:46,772 --> 00:48:48,230
what are the
transduction channels?

851
00:48:48,230 --> 00:48:49,900
How do the tip links work?

852
00:48:49,900 --> 00:48:51,150
How are they mechanosensitive?

853
00:48:54,170 --> 00:48:55,730
OK, now let's talk.

854
00:48:55,730 --> 00:48:58,450
We've been alluding to the two
types of hair cells, right?

855
00:48:58,450 --> 00:48:59,785
Outer and inner hair cells.

856
00:49:01,660 --> 00:49:07,160
And all mammals
have these two types

857
00:49:07,160 --> 00:49:08,910
of hair cells, outer
and inner hair cells.

858
00:49:10,480 --> 00:49:16,060
Birds have hair cells that
are also of several classes.

859
00:49:16,060 --> 00:49:19,380
They have what are called
tall and short hair cells.

860
00:49:19,380 --> 00:49:22,640
They're a little bit different
than outer and inner hair

861
00:49:22,640 --> 00:49:23,140
cells.

862
00:49:23,140 --> 00:49:26,350
Reptiles generally have
one type of hair cell.

863
00:49:26,350 --> 00:49:31,480
So the inner and outer hair cell
distinction is true for mammals

864
00:49:31,480 --> 00:49:31,980
mainly.

865
00:49:33,020 --> 00:49:34,460
So how do they get their names?

866
00:49:34,460 --> 00:49:38,070
Well, if you look down on the
top of the organ of Corti--

867
00:49:38,070 --> 00:49:40,110
so this is my wire model.

868
00:49:40,110 --> 00:49:42,540
So this is like the cochlea
we've been looking at.

869
00:49:42,540 --> 00:49:45,640
Now, turn it so you're looking
down from the apex down.

870
00:49:45,640 --> 00:49:48,730
On top of this
membrane, what you

871
00:49:48,730 --> 00:49:52,200
would see if you looked
at one little tiny piece

872
00:49:52,200 --> 00:49:56,020
is a row of inner hair cells
going from the extreme base

873
00:49:56,020 --> 00:50:00,810
to the apex, which would
be this row right here.

874
00:50:00,810 --> 00:50:04,030
And three rows of outer hair
cells, going from the base

875
00:50:04,030 --> 00:50:07,520
to the apex, and it turns
out that the inner hair

876
00:50:07,520 --> 00:50:09,020
cells get their
name because they're

877
00:50:09,020 --> 00:50:10,900
on the inner side of the spiral.

878
00:50:12,310 --> 00:50:16,970
And the outers are on the
outer part of the spiral.

879
00:50:16,970 --> 00:50:19,360
So the inners are
toward the center,

880
00:50:19,360 --> 00:50:21,080
or toward the axis
of the cochlea.

881
00:50:22,270 --> 00:50:24,000
The outers are away from it.

882
00:50:26,250 --> 00:50:29,870
And this view,
looking down on them,

883
00:50:29,870 --> 00:50:32,620
would be looking down
onto their stereocilia.

884
00:50:32,620 --> 00:50:35,985
And these white structures are
the hair bundles-- the tips,

885
00:50:35,985 --> 00:50:37,430
if you will-- of
the stereocilia.

886
00:50:38,970 --> 00:50:44,010
And there's one, two, three,
four, five, six, seven, eight

887
00:50:44,010 --> 00:50:47,060
and a half inner
hair cells here.

888
00:50:47,060 --> 00:50:49,600
And in the first row
of outer hair cells,

889
00:50:49,600 --> 00:50:53,636
there's one, two, three, four,
five, six, seven, eight, nine,

890
00:50:53,636 --> 00:50:55,090
ten, eleven, twelve.

891
00:50:55,090 --> 00:50:57,530
There's a dozen
outer hair cells.

892
00:50:57,530 --> 00:50:59,750
And their stereocilia
are lined up differently.

893
00:50:59,750 --> 00:51:03,570
They're sort of like inverted
V's on the outer hair cells.

894
00:51:03,570 --> 00:51:06,500
And there's the first
row, the second row,

895
00:51:06,500 --> 00:51:10,470
and the outermost row, the
third row of outer hair cells.

896
00:51:10,470 --> 00:51:12,870
And this is a
stereotyped pattern.

897
00:51:12,870 --> 00:51:15,080
Almost all mammals have this.

898
00:51:15,080 --> 00:51:18,540
In the human, if you go up
into the apex of the cochlea,

899
00:51:18,540 --> 00:51:21,980
sometimes a fourth row of outer
hair cells starts to form,

900
00:51:21,980 --> 00:51:25,000
but it's not very
well organized.

901
00:51:25,000 --> 00:51:26,180
It's sort of patchy.

902
00:51:26,180 --> 00:51:29,002
But you can have a fourth
row of outer hair cells.

903
00:51:31,600 --> 00:51:37,820
If one of these were missing,
the supporting cells nearby

904
00:51:37,820 --> 00:51:40,155
form a little scar in its place.

905
00:51:42,100 --> 00:51:45,080
And we'll talk about things that
kill hair cells in a few weeks.

906
00:51:46,680 --> 00:51:49,485
Loud sounds can kill
your hair cells.

907
00:51:50,670 --> 00:51:53,179
Infectious agents--
meningitis, for example--

908
00:51:53,179 --> 00:51:54,220
can kill your hair cells.

909
00:51:54,220 --> 00:51:58,340
Certain drugs, aminoglycoside
antibiotics like kanamycin

910
00:51:58,340 --> 00:51:59,450
can kill your hair cells.

911
00:52:00,550 --> 00:52:04,850
And the supporting cells
thereby just fill in.

912
00:52:04,850 --> 00:52:08,850
And you can go and look at a
cochlea that has some hair cell

913
00:52:08,850 --> 00:52:09,350
damage.

914
00:52:09,350 --> 00:52:11,540
You can count, you
can see how regular

915
00:52:11,540 --> 00:52:14,020
the array is of hair cells.

916
00:52:14,020 --> 00:52:15,939
And you can count how
many are present there

917
00:52:15,939 --> 00:52:16,980
and how many are damaged.

918
00:52:18,139 --> 00:52:19,680
And you can, you
know, say if there's

919
00:52:19,680 --> 00:52:22,450
a 50% loss of outer
hair cells in row one,

920
00:52:22,450 --> 00:52:24,460
this regularity is so beautiful.

921
00:52:26,300 --> 00:52:30,220
Unfortunately, once
they're killed in a mammal,

922
00:52:30,220 --> 00:52:31,650
they never come back.

923
00:52:31,650 --> 00:52:35,820
You cannot regrow your hair
cells once they've been killed.

924
00:52:35,820 --> 00:52:39,560
In birds, they grow right back.

925
00:52:39,560 --> 00:52:41,000
Takes about three or four weeks.

926
00:52:42,730 --> 00:52:46,134
So you can kill all the
hair cells in a bird cochlea

927
00:52:46,134 --> 00:52:47,800
and come back three
or four weeks later,

928
00:52:47,800 --> 00:52:48,924
and they're all grown back.

929
00:52:50,230 --> 00:52:52,780
In mammals, they
don't grow back.

930
00:52:52,780 --> 00:52:54,591
And so there's a
lot of interest--

931
00:52:54,591 --> 00:52:57,090
Because you have these agents
that kill hair cells-- there's

932
00:52:57,090 --> 00:53:00,600
a lot of interest in, how
can we make our hair cells

933
00:53:00,600 --> 00:53:02,255
grow back after
they've been killed?

934
00:53:03,270 --> 00:53:06,430
And people are thinking
of stem cell approached

935
00:53:06,430 --> 00:53:11,190
or neurotropic drugs
that might be good.

936
00:53:11,190 --> 00:53:13,070
So why don't they grow back?

937
00:53:13,070 --> 00:53:15,220
We don't know that at all.

938
00:53:15,220 --> 00:53:17,950
We do know that,
for example, I'm

939
00:53:17,950 --> 00:53:21,110
in a department called
ENT-- Ear, Nose, and Throat.

940
00:53:21,110 --> 00:53:23,840
Lots of the surgeons
in our department deal

941
00:53:23,840 --> 00:53:26,700
with cancers of the
head and neck, right?

942
00:53:26,700 --> 00:53:30,730
Because there are cancers
that can come up, and surgeons

943
00:53:30,730 --> 00:53:33,950
can take care of that
by taking cancers out.

944
00:53:33,950 --> 00:53:37,050
There are no known cancers
that grow in the inner ear.

945
00:53:37,050 --> 00:53:38,390
It never, ever happens.

946
00:53:40,030 --> 00:53:44,570
So maybe these cells are
so far differentiated

947
00:53:44,570 --> 00:53:47,420
and they've become this
classic inner and outer hair

948
00:53:47,420 --> 00:53:51,110
distinction, they're so evolved
that they can't grow back.

949
00:53:51,110 --> 00:53:52,120
They can't multiply.

950
00:53:52,120 --> 00:53:53,390
They can't form a cancer.

951
00:53:53,390 --> 00:53:57,750
But unfortunately, once
there destroyed by some agent

952
00:53:57,750 --> 00:54:01,140
like a drug, they
can't grow back.

953
00:54:01,140 --> 00:54:05,950
So a way to put new
cells in there that

954
00:54:05,950 --> 00:54:09,040
could become new
hair cells, or a way

955
00:54:09,040 --> 00:54:12,100
to encourage these
supporting cells on the sides

956
00:54:12,100 --> 00:54:15,720
to grow and become hair cells,
is a very interesting idea,

957
00:54:15,720 --> 00:54:18,790
but one that's just in
the research phase now.

958
00:54:20,830 --> 00:54:24,250
OK, so that's the difference
between inner and outer hair

959
00:54:24,250 --> 00:54:25,000
cells.

960
00:54:25,000 --> 00:54:27,175
If you cut them in
the other dimension

961
00:54:27,175 --> 00:54:29,940
and look at them in
the longitudinal plane,

962
00:54:29,940 --> 00:54:33,960
inner and outer hair cells
look completely different.

963
00:54:33,960 --> 00:54:37,280
An inner hair cell
is a big fat cell.

964
00:54:37,280 --> 00:54:39,300
It comes up to a
neck and bulges out

965
00:54:39,300 --> 00:54:41,675
a little bit where the hair
bundle is, way up at the top.

966
00:54:44,630 --> 00:54:46,420
At the bottom of
the inner hair cell,

967
00:54:46,420 --> 00:54:49,700
there's lots of
afferent nerve endings.

968
00:54:50,880 --> 00:54:53,510
Maybe as many as
20 per hair cell.

969
00:54:55,360 --> 00:54:57,570
There's a few efferent
nerve endings,

970
00:54:57,570 --> 00:54:59,835
but they're usually not
on the hair cell itself.

971
00:55:00,970 --> 00:55:03,412
They're on these
afferent terminals.

972
00:55:03,412 --> 00:55:05,620
The efferents come and get
on the afferent terminals.

973
00:55:08,550 --> 00:55:10,300
The outer hair
cells, by contrast,

974
00:55:10,300 --> 00:55:11,690
are completely different.

975
00:55:11,690 --> 00:55:14,845
They're long, test
tube-like shaped cells.

976
00:55:16,740 --> 00:55:19,370
Down at the bottom, they
also have nerve terminals.

977
00:55:19,370 --> 00:55:21,460
Most of the nerve
terminals in this case

978
00:55:21,460 --> 00:55:23,990
are efferent nerve terminals.

979
00:55:23,990 --> 00:55:26,850
How do we know that
they're efferent afferent?

980
00:55:34,290 --> 00:55:40,630
Well, if you look at them
in the electron microscope--

981
00:55:40,630 --> 00:55:43,560
I'll just draw a quick diagram.

982
00:55:45,120 --> 00:55:46,140
Here's the hair cell.

983
00:55:50,720 --> 00:55:52,290
Here's a nerve
terminal coming up.

984
00:55:54,890 --> 00:55:59,310
And here is a whole bunch
of synaptic vesicles

985
00:55:59,310 --> 00:56:05,670
in the hair cell ready to
be released when the hair

986
00:56:05,670 --> 00:56:07,880
cell is stimulated with sound.

987
00:56:07,880 --> 00:56:09,820
Obviously, the transmission
is going that way.

988
00:56:12,180 --> 00:56:13,660
Here's a nerve terminal.

989
00:56:19,880 --> 00:56:22,710
Here's a whole bunch
of synaptic vesicles.

990
00:56:28,450 --> 00:56:30,670
None over here, they're
all on the nerve terminal.

991
00:56:32,180 --> 00:56:36,440
When the message comes
down from the brain,

992
00:56:36,440 --> 00:56:37,950
a whole bunch of
these vesicles are

993
00:56:37,950 --> 00:56:40,940
released onto the hair cell.

994
00:56:40,940 --> 00:56:44,910
OK, so by just looking at the
nerve terminals in the electron

995
00:56:44,910 --> 00:56:49,360
microscope, you can get
an idea of which direction

996
00:56:49,360 --> 00:56:50,500
the transmission is going.

997
00:56:50,500 --> 00:56:53,390
And so label them as either
afferent or efferent.

998
00:56:53,390 --> 00:56:56,590
On the outer hair cells, there
are many, many efferent nerve

999
00:56:56,590 --> 00:56:57,600
terminals on them.

1000
00:57:01,830 --> 00:57:05,790
In fact, in the
1970s, it became clear

1001
00:57:05,790 --> 00:57:09,950
that almost all afferent
nerve fibers, the ones that

1002
00:57:09,950 --> 00:57:12,330
were sending messages
to the brain,

1003
00:57:12,330 --> 00:57:16,200
were associated with the inner
hair cells, and only about 5%

1004
00:57:16,200 --> 00:57:18,610
of them were associated
with the outer hair cells.

1005
00:57:18,610 --> 00:57:22,750
This is was a big
mystery for a while,

1006
00:57:22,750 --> 00:57:24,560
and people didn't
believe it at first.

1007
00:57:24,560 --> 00:57:26,250
It said, well, all
the information going

1008
00:57:26,250 --> 00:57:28,120
into the brain, or
95% percent of it,

1009
00:57:28,120 --> 00:57:29,980
is coming from the
inner hair cell.

1010
00:57:29,980 --> 00:57:31,660
Huh, that's kind of funny.

1011
00:57:31,660 --> 00:57:35,180
There's actually more outer hair
cells than inner hair cells.

1012
00:57:35,180 --> 00:57:36,100
So what's going on?

1013
00:57:36,100 --> 00:57:37,870
Somebody screwed up
the counts, right?

1014
00:57:37,870 --> 00:57:40,172
So it was done over
and over again,

1015
00:57:40,172 --> 00:57:41,630
and the counts came
back correctly.

1016
00:57:43,540 --> 00:57:45,130
So how do we interpret that now?

1017
00:57:45,130 --> 00:57:50,230
Well, about the same time in the
early 1980s, a very interesting

1018
00:57:50,230 --> 00:57:52,455
property of outer hair
cells was noticed.

1019
00:57:55,090 --> 00:57:58,990
It was noticed that outer hair
cells are actually motile.

1020
00:57:58,990 --> 00:57:59,725
They can move.

1021
00:58:01,970 --> 00:58:08,040
And this was first discovered
by Joe Santos Saatchi and others

1022
00:58:08,040 --> 00:58:11,240
in the early 1980s.

1023
00:58:11,240 --> 00:58:20,660
And this discovery was made
when they put a hair cell

1024
00:58:20,660 --> 00:58:24,320
in a fluid of high potassium,
lots of potassium here.

1025
00:58:26,280 --> 00:58:27,830
There are some
potassium channels

1026
00:58:27,830 --> 00:58:29,060
in the sides of the cell.

1027
00:58:29,060 --> 00:58:29,950
Potassium went in.

1028
00:58:31,070 --> 00:58:34,430
When you have positive
ions coming into a cell,

1029
00:58:34,430 --> 00:58:35,810
the cell depolarizes.

1030
00:58:35,810 --> 00:58:38,850
It might have started out
at minus 80 millivolts.

1031
00:58:38,850 --> 00:58:42,740
In the high potassium solution,
it may have gone to minus 50

1032
00:58:42,740 --> 00:58:45,285
millivolts or maybe
even 0 millivolts.

1033
00:58:48,160 --> 00:58:51,050
Bill Brownell and Joe Santos,
when they saw this happen,

1034
00:58:51,050 --> 00:58:53,075
they saw the cell shrink.

1035
00:58:54,810 --> 00:58:57,910
It was, let's say, five
micrometers in length before.

1036
00:58:57,910 --> 00:59:00,475
They put it in the potassium
solution, it became four.

1037
00:59:02,270 --> 00:59:04,420
Take it out of the high
potassium solution,

1038
00:59:04,420 --> 00:59:06,870
put it in a regular solution,
it lengthened again.

1039
00:59:08,322 --> 00:59:12,940
OK, here is a graph
of those data.

1040
00:59:14,820 --> 00:59:17,920
In this case it's a more elegant
experiment where they actually

1041
00:59:17,920 --> 00:59:21,460
measured the potential
inside the cell

1042
00:59:21,460 --> 00:59:23,260
by putting an electrode into it.

1043
00:59:30,140 --> 00:59:34,510
So you can run this
out to your amplifier

1044
00:59:34,510 --> 00:59:37,370
and measure the
electrical potential

1045
00:59:37,370 --> 00:59:40,350
in terms of the millivolts
of the inside of the cell.

1046
00:59:41,560 --> 00:59:46,260
And by putting current down
or coming out of the cell,

1047
00:59:46,260 --> 00:59:50,390
you can move the inside of this
potential whatever you want,

1048
00:59:50,390 --> 00:59:51,470
whichever way you want.

1049
00:59:52,530 --> 00:59:57,920
And in this case, this
x-axis in millivolts

1050
00:59:57,920 --> 01:00:00,510
is the potential
inside the hair cell.

1051
01:00:03,000 --> 01:00:07,020
The ordinary potential is
about minus 80 millivolts,

1052
01:00:07,020 --> 01:00:08,870
about right here.

1053
01:00:08,870 --> 01:00:13,900
Minus 180 is a huge
hyperpolarization of the cell.

1054
01:00:13,900 --> 01:00:17,440
And plus 0 up to
plus 40 millivolts

1055
01:00:17,440 --> 01:00:19,041
is a depolarization of a cell.

1056
01:00:19,041 --> 01:00:21,040
Does everybody understand
what we're doing here?

1057
01:00:21,040 --> 01:00:24,160
We're changing the
intracellular potential

1058
01:00:24,160 --> 01:00:25,905
of the cell in terms
of its millivolts.

1059
01:00:28,670 --> 01:00:31,470
And then we're looking
at the change in length.

1060
01:00:31,470 --> 01:00:33,850
As you depolarize
the cell, the cell

1061
01:00:33,850 --> 01:00:37,020
goes from 0 to negative values.

1062
01:00:37,020 --> 01:00:39,620
That's a shortening in
terms of micrometers

1063
01:00:39,620 --> 01:00:41,580
of the length of
the outer hair cell.

1064
01:00:41,580 --> 01:00:44,870
This is the basal end
where the hair cells are,

1065
01:00:44,870 --> 01:00:47,560
this is the apical end where
the stereocilia would be.

1066
01:00:48,880 --> 01:00:51,310
OK, so these hair cells
can actually move.

1067
01:00:51,310 --> 01:00:54,410
You can do this experiment
with a muscle fiber

1068
01:00:54,410 --> 01:00:55,565
and get the same result.

1069
01:00:56,920 --> 01:00:59,190
It's a very different
process, but when

1070
01:00:59,190 --> 01:01:04,806
you depolarize a muscle cell,
it contracts by actin and myosin

1071
01:01:04,806 --> 01:01:05,305
means.

1072
01:01:06,360 --> 01:01:10,050
This was very surprising though
to see this in a sensory cell.

1073
01:01:10,050 --> 01:01:13,610
Sensory cells aren't
supposed to contract, right?

1074
01:01:13,610 --> 01:01:15,030
They figured out that they are.

1075
01:01:15,030 --> 01:01:15,860
They can contract.

1076
01:01:17,400 --> 01:01:23,310
Now, that means this
outer hair cell--

1077
01:01:23,310 --> 01:01:25,050
and I should say
outer hair cell,

1078
01:01:25,050 --> 01:01:27,350
these are outer hair
cells because when

1079
01:01:27,350 --> 01:01:30,990
you do the same experiment
with an inner hair cell

1080
01:01:30,990 --> 01:01:34,100
or any other cell in the body,
you don't get a contraction.

1081
01:01:34,100 --> 01:01:36,260
So it's peculiar to
outer hair cells.

1082
01:01:36,260 --> 01:01:37,360
Make sure you know that.

1083
01:01:37,360 --> 01:01:39,470
Outer hair cells are the
ones that are motile.

1084
01:01:41,480 --> 01:01:44,010
This process became
known as electromotility.

1085
01:01:54,830 --> 01:02:02,710
OK, so when the inside
voltage is changed,

1086
01:02:02,710 --> 01:02:05,070
the length of the outer
hair cells has changed.

1087
01:02:05,070 --> 01:02:07,270
So let me give you a
demonstration of this.

1088
01:02:07,270 --> 01:02:11,720
I have a nice demonstration
from Joe Santos Saatchi, who

1089
01:02:11,720 --> 01:02:13,900
is now at Yale
School of Medicine.

1090
01:02:13,900 --> 01:02:16,210
And he made this demonstration.

1091
01:02:17,320 --> 01:02:19,290
And it's kind of a
clever demonstration

1092
01:02:19,290 --> 01:02:21,880
because you can
see the hair cell,

1093
01:02:21,880 --> 01:02:27,080
and it will be moving because
Joe has patched onto the hair

1094
01:02:27,080 --> 01:02:28,530
cell with his electrode.

1095
01:02:29,770 --> 01:02:32,990
And the electrode is-- usually,
in these kinds of experiments--

1096
01:02:32,990 --> 01:02:36,240
is put on a micromanipulator
and it's bolted to the table.

1097
01:02:37,270 --> 01:02:40,960
And because that patch
pipette has impaled the cell,

1098
01:02:40,960 --> 01:02:43,070
that part of the
cell is just pegged

1099
01:02:43,070 --> 01:02:45,400
so it's not going
to move at all.

1100
01:02:45,400 --> 01:02:46,940
That's the very
bottom of the cell.

1101
01:02:46,940 --> 01:02:49,540
And you'll see a little bit
of a ghost-like image of that.

1102
01:02:49,540 --> 01:02:53,610
The rest of the cell is the long
part of the hair cell, and then

1103
01:02:53,610 --> 01:02:56,510
the stereocilia, or hair
bundle, right up at the top.

1104
01:02:57,630 --> 01:03:00,200
And that part is free to move.

1105
01:03:00,200 --> 01:03:03,640
Now, what Joe has done is he's
depolarized and hyperpolarized

1106
01:03:03,640 --> 01:03:04,885
the cell using his amplifier.

1107
01:03:06,050 --> 01:03:13,620
But he has made that signal
sync'd to a musical signal, OK?

1108
01:03:13,620 --> 01:03:15,800
So you'll hear music
on the soundtrack

1109
01:03:15,800 --> 01:03:17,660
and you'll see the
hair cell moving.

1110
01:03:17,660 --> 01:03:20,890
The music is not directly
stimulating the hair cell

1111
01:03:20,890 --> 01:03:24,320
by moving its stereocilia
as normally it would be,

1112
01:03:24,320 --> 01:03:26,870
as when we listen to it.

1113
01:03:26,870 --> 01:03:31,480
Instead, that music is just in
sync with the electrical signal

1114
01:03:31,480 --> 01:03:33,830
manipulating the inside
of the hair cell.

1115
01:03:33,830 --> 01:03:34,910
So I'll play that now.

1116
01:03:38,403 --> 01:03:39,401
Once again.

1117
01:03:42,900 --> 01:03:44,625
OK, so here's the hair cell.

1118
01:03:45,970 --> 01:03:49,803
This is the shadow of the
electrode holding this stiff.

1119
01:03:50,830 --> 01:03:53,070
This is the main
part of the cell.

1120
01:03:53,070 --> 01:03:54,974
These are the stereocilia
right up there.

1121
01:04:25,030 --> 01:04:25,530
OK.

1122
01:04:26,900 --> 01:04:31,330
So apparently Joe, lectures
to medical students,

1123
01:04:31,330 --> 01:04:35,110
says there's a reflex that goes
directly from your hair cells

1124
01:04:35,110 --> 01:04:36,830
to your dancing feet.

1125
01:04:36,830 --> 01:04:38,960
And apparently, the medical
students believe him.

1126
01:04:40,510 --> 01:04:44,500
Anyway, that is
clearly a demonstration

1127
01:04:44,500 --> 01:04:51,020
that this electromotility is
much faster than, for example,

1128
01:04:51,020 --> 01:04:52,690
the contraction of muscle cells.

1129
01:04:52,690 --> 01:04:55,190
Muscle cell contraction, put
it in a dish, or even hair cell

1130
01:04:55,190 --> 01:04:58,990
in a dish-- it can be very slow.

1131
01:04:58,990 --> 01:05:02,680
This electromotility is
happening at audio frequencies,

1132
01:05:02,680 --> 01:05:03,700
right?

1133
01:05:03,700 --> 01:05:07,500
Some of those sounds were
thousands of times per second.

1134
01:05:07,500 --> 01:05:12,340
So in the early debate
of electromotility,

1135
01:05:12,340 --> 01:05:15,920
there were some questions
of how fast this is

1136
01:05:15,920 --> 01:05:18,620
and whether it really
manipulates movement

1137
01:05:18,620 --> 01:05:20,340
of the hair cells
at audio frequency.

1138
01:05:20,340 --> 01:05:22,710
And I think that
kind of demonstration

1139
01:05:22,710 --> 01:05:25,000
clearly shows that it does.

1140
01:05:25,000 --> 01:05:26,810
So what good is this?

1141
01:05:26,810 --> 01:05:29,330
How does this help us
in the sense of hearing?

1142
01:05:30,440 --> 01:05:34,940
And what good would it be to
have a motile sensory cell?

1143
01:05:34,940 --> 01:05:41,110
Well, the idea is that these
hair cells-- here again

1144
01:05:41,110 --> 01:05:43,880
are the inner hair cells and the
three rows of outer hair cells.

1145
01:05:45,250 --> 01:05:47,180
Sound comes into the ear.

1146
01:05:47,180 --> 01:05:49,570
It moves these membranes.

1147
01:05:49,570 --> 01:05:50,790
It moves the hair bundles.

1148
01:05:52,000 --> 01:05:55,640
Motion of the hair bundles opens
up these transducer channels

1149
01:05:55,640 --> 01:05:59,620
which allow ions to come in
and depolarize the outer hair

1150
01:05:59,620 --> 01:06:00,450
cells, let's say.

1151
01:06:01,550 --> 01:06:04,845
When the outer hair cells are
depolarized, they shorten.

1152
01:06:06,330 --> 01:06:09,330
OK, when the sound
phase reverses,

1153
01:06:09,330 --> 01:06:12,820
the hair bundle moves the
other way, the channels close.

1154
01:06:12,820 --> 01:06:15,486
The hair cells go back
to their normal length.

1155
01:06:15,486 --> 01:06:17,610
And this goes back and
forth, and in the outer hair

1156
01:06:17,610 --> 01:06:19,151
cells are getting
longer and shorter.

1157
01:06:20,670 --> 01:06:24,940
Somehow, that motion,
that mechanical energy,

1158
01:06:24,940 --> 01:06:28,930
adds to the vibration
that was initiated

1159
01:06:28,930 --> 01:06:32,135
by the sound in a sort of
an amplification mechanism.

1160
01:06:33,270 --> 01:06:35,870
So you then have more vibration.

1161
01:06:35,870 --> 01:06:38,820
You then have more bending
of the stereocilia.

1162
01:06:38,820 --> 01:06:41,430
You have more depolarizing
of the hair cells.

1163
01:06:41,430 --> 01:06:44,140
You have even more
electromotility and sort

1164
01:06:44,140 --> 01:06:46,250
of a positive
feedback loop here.

1165
01:06:47,540 --> 01:06:49,830
The outer hair cells
then are sometimes

1166
01:06:49,830 --> 01:06:52,180
called the cochlear amplifier.

1167
01:06:52,180 --> 01:06:57,710
They amplify the vibration
patterns set up by sound

1168
01:06:57,710 --> 01:06:59,100
in the cochlea.

1169
01:06:59,100 --> 01:07:02,880
So the outer hair
cells are sometimes

1170
01:07:02,880 --> 01:07:05,332
nicknamed the
cochlear amplifier.

1171
01:07:11,590 --> 01:07:13,250
So what good is a
cochlear amplifier?

1172
01:07:14,440 --> 01:07:18,700
Well, you have this ordinary
receptor cell over here.

1173
01:07:18,700 --> 01:07:20,840
It doesn't change
its length at all,

1174
01:07:20,840 --> 01:07:24,560
but it has all the auditory
nerve fibers linked to it.

1175
01:07:24,560 --> 01:07:28,190
Now instead of its stereocilia
moving just a little bit,

1176
01:07:28,190 --> 01:07:31,325
it has an amplifier sitting
right next to it and amplifies

1177
01:07:31,325 --> 01:07:32,850
to all these membranes.

1178
01:07:32,850 --> 01:07:34,470
And the inner hair
cell stereocilia

1179
01:07:34,470 --> 01:07:36,380
are really now waving
and back and forth.

1180
01:07:38,060 --> 01:07:41,980
They then send their messages
to the auditory nerve fibers,

1181
01:07:41,980 --> 01:07:45,620
which send their axons and
messages into the brain.

1182
01:07:45,620 --> 01:07:48,400
Your brain says, I hear sound.

1183
01:07:48,400 --> 01:07:50,530
Even when it's a
very soft sound,

1184
01:07:50,530 --> 01:07:54,650
like a pin dropping-- which,
without the cochlear amplifier,

1185
01:07:54,650 --> 01:07:57,290
would be inaudible--
that pin dropping,

1186
01:07:57,290 --> 01:07:59,893
that very small mechanical
motion is amplified.

1187
01:08:01,540 --> 01:08:03,270
And the inner hair
cells then say,

1188
01:08:03,270 --> 01:08:04,670
oh, yes I do hear the sound.

1189
01:08:06,430 --> 01:08:10,120
So the function then
of these receptor cells

1190
01:08:10,120 --> 01:08:12,420
is very different
than what you have

1191
01:08:12,420 --> 01:08:15,510
in vision, where you had
rods and cones, right?

1192
01:08:15,510 --> 01:08:18,725
Rods and cones mediate
different types of vision.

1193
01:08:20,279 --> 01:08:24,279
In the cochlea, the hair
cells work together.

1194
01:08:24,279 --> 01:08:26,540
The outer hair cells ore
the cochlear amplifier

1195
01:08:26,540 --> 01:08:30,800
making this thing amplified
more, and more sensitive.

1196
01:08:30,800 --> 01:08:35,189
The inner hair cells then
are the major receptor cells

1197
01:08:35,189 --> 01:08:38,050
that are sending their
messages to the brain, OK?

1198
01:08:38,050 --> 01:08:44,270
So it's really a different
kind of two receptor sense,

1199
01:08:44,270 --> 01:08:46,040
if you will, compared to vision.

1200
01:08:49,649 --> 01:08:57,290
And that's what this
diagram is supposed to be.

1201
01:08:57,290 --> 01:09:00,069
This is very fanciful diagram.

1202
01:09:00,069 --> 01:09:03,660
And there's a lot of hand
waving here associated

1203
01:09:03,660 --> 01:09:05,949
with how the cochlear
amplifier really works.

1204
01:09:08,830 --> 01:09:13,359
This is an unraveled cochlea
from the base to the apex,

1205
01:09:13,359 --> 01:09:15,290
and this is how
much displacement

1206
01:09:15,290 --> 01:09:18,370
you have-- von Bekesy's
traveling wave envelope,

1207
01:09:18,370 --> 01:09:19,609
if you will.

1208
01:09:19,609 --> 01:09:22,990
This dashed line is what would
happen if you just put sound in

1209
01:09:22,990 --> 01:09:24,219
and there was no amplifier.

1210
01:09:26,279 --> 01:09:30,840
And this enhanced solid line
is when you have the outer hair

1211
01:09:30,840 --> 01:09:33,865
cells working their
cochlear amplifier magic.

1212
01:09:35,340 --> 01:09:37,560
And apparently,
the active region

1213
01:09:37,560 --> 01:09:39,830
where the outer hair
cells are most active

1214
01:09:39,830 --> 01:09:44,930
is just basal to the peak
of this traveling wave.

1215
01:09:44,930 --> 01:09:46,290
And how do we know that?

1216
01:09:46,290 --> 01:09:49,229
How do we know that the
outer hair cell cochlear

1217
01:09:49,229 --> 01:09:51,750
amplifier is very important?

1218
01:09:51,750 --> 01:09:55,140
Well, there are
actually situations

1219
01:09:55,140 --> 01:09:59,070
when you can lose
your outer hair cells

1220
01:09:59,070 --> 01:10:04,380
and you have pretty intact
inner hair cell population.

1221
01:10:04,380 --> 01:10:13,720
So in an animal treated with
the aminoglycocide kanamycin,

1222
01:10:13,720 --> 01:10:15,370
it turns out that
the outer hair cells

1223
01:10:15,370 --> 01:10:18,640
are a little bit more
sensitive to the kanamycin

1224
01:10:18,640 --> 01:10:20,990
then the inner hair cells are.

1225
01:10:20,990 --> 01:10:23,460
So if you treat with
just the right dose,

1226
01:10:23,460 --> 01:10:25,890
you can find a
place of the cochlea

1227
01:10:25,890 --> 01:10:28,446
where there are intact
inner hair cells

1228
01:10:28,446 --> 01:10:30,695
and where the outer hair
cells have all been lesioned.

1229
01:10:32,340 --> 01:10:35,920
Basal to that, for example,
all the hair cells are gone.

1230
01:10:35,920 --> 01:10:38,869
And apical to that, none
of the hair cells are gone.

1231
01:10:38,869 --> 01:10:40,410
So in a certain
region of the cochlea

1232
01:10:40,410 --> 01:10:42,240
with just the right
dose of kanamycin.

1233
01:10:43,710 --> 01:10:47,040
And in those areas, where you
just have inner hair cells

1234
01:10:47,040 --> 01:10:49,960
without the outer hair cells,
you have a huge hearing loss.

1235
01:10:49,960 --> 01:10:50,915
You're not deaf.

1236
01:10:52,040 --> 01:10:54,570
The inner hair cells
are still there

1237
01:10:54,570 --> 01:10:57,560
and they're sending their
messages to the brain

1238
01:10:57,560 --> 01:10:59,310
by their auditory nerve fibers.

1239
01:10:59,310 --> 01:11:01,620
But there's a big
hearing loss because you

1240
01:11:01,620 --> 01:11:04,105
have lost the function of
the cohclear amplifier.

1241
01:11:05,560 --> 01:11:11,120
And those experiments were
done in the 1970s and '80s.

1242
01:11:11,120 --> 01:11:14,220
And they were
criticized by saying,

1243
01:11:14,220 --> 01:11:17,410
well, anytime you do
some lesion treatment,

1244
01:11:17,410 --> 01:11:19,970
you say you have normal
inner hair cells and outers.

1245
01:11:19,970 --> 01:11:23,090
Well, you don't really know the
inner hair cells are normal.

1246
01:11:23,090 --> 01:11:24,620
Maybe the drug affected them.

1247
01:11:24,620 --> 01:11:26,670
They're still there,
but they're screwed up.

1248
01:11:27,850 --> 01:11:34,770
So recently, a much
more elegant way

1249
01:11:34,770 --> 01:11:37,450
of doing that same sort
of experiment has come up.

1250
01:11:37,450 --> 01:11:41,680
And this is the paper,
the research paper,

1251
01:11:41,680 --> 01:11:44,455
that is assigned reading
for today's lecture.

1252
01:11:47,130 --> 01:11:52,330
It turns out you can knock
out the cochlear amplifier

1253
01:11:52,330 --> 01:11:56,740
by knocking out a particular
protein in the outer hair cells

1254
01:11:56,740 --> 01:11:59,030
and have the outer
hair cells still there.

1255
01:12:00,330 --> 01:12:06,050
And this work started
out with the discovery

1256
01:12:06,050 --> 01:12:12,875
of a protein that's in the
membrane of the outer hair

1257
01:12:12,875 --> 01:12:13,375
cells.

1258
01:12:15,170 --> 01:12:16,860
So if you look at
the outer hair cells,

1259
01:12:16,860 --> 01:12:19,665
there's a lot of
protein in the membrane.

1260
01:12:32,190 --> 01:12:36,340
And the protein is found pretty
much nowhere else in the body

1261
01:12:36,340 --> 01:12:38,695
and was given the name prestin.

1262
01:12:41,330 --> 01:12:45,170
Now, you amateur musicians out
there, when you play a piece--

1263
01:12:45,170 --> 01:12:46,830
right?-- at the
beginning of the piece,

1264
01:12:46,830 --> 01:12:50,240
at least for classical
music, the composer gives you

1265
01:12:50,240 --> 01:12:54,130
an Italian word that says how
fast you should play it, right?

1266
01:12:54,130 --> 01:12:57,730
And if it says largo, you're
supposed to play it really

1267
01:12:57,730 --> 01:13:01,190
slowly, Right or
adagio, slow, right?

1268
01:13:01,190 --> 01:13:03,985
What's the marking or
Italian word for "fast"?

1269
01:13:03,985 --> 01:13:04,980
AUDIENCE: Presto.

1270
01:13:04,980 --> 01:13:06,320
PROFESSOR: Presto, right.

1271
01:13:08,650 --> 01:13:11,770
And this protein
was named prestin

1272
01:13:11,770 --> 01:13:14,690
because, at least at the
time it was discovered,

1273
01:13:14,690 --> 01:13:16,350
they had the idea that, oh, OK.

1274
01:13:16,350 --> 01:13:19,360
Maybe it's the cochlear
amplifier protein

1275
01:13:19,360 --> 01:13:22,360
and it makes these outer hair
cells shorten and contract

1276
01:13:22,360 --> 01:13:24,304
really quickly, very fast.

1277
01:13:24,304 --> 01:13:25,345
So we'll call it prestin.

1278
01:13:28,110 --> 01:13:30,290
It turned out that
that was true,

1279
01:13:30,290 --> 01:13:33,710
and here's some of the
evidence in support of that.

1280
01:13:33,710 --> 01:13:37,490
You can knock out
the gene for prestin.

1281
01:13:37,490 --> 01:13:44,260
So a knock-out is an animal
in which a particular gene

1282
01:13:44,260 --> 01:13:49,040
is either removed or made so
it doesn't make the protein.

1283
01:13:49,040 --> 01:13:52,040
Part of it's deleted, and
so the protein is not made.

1284
01:13:52,040 --> 01:13:55,150
You can make a
knock-out mouse where

1285
01:13:55,150 --> 01:13:57,120
the prestin is knocked out.

1286
01:13:57,120 --> 01:13:59,374
And that's what was
done in this paper.

1287
01:14:06,020 --> 01:14:11,710
OK, and in that knock-out
mouse, you can look--

1288
01:14:11,710 --> 01:14:14,700
and they looked at a
whole bunch of things.

1289
01:14:14,700 --> 01:14:18,720
That looked at the
electromotility the outer hair

1290
01:14:18,720 --> 01:14:19,220
cells.

1291
01:14:19,220 --> 01:14:21,395
So they took outer hair
cells and put them in a dish

1292
01:14:21,395 --> 01:14:24,350
and looked at the kind of
movements we saw in that video.

1293
01:14:25,520 --> 01:14:28,270
And in this trace,
this is minus minus,

1294
01:14:28,270 --> 01:14:32,940
which is the geneticist
lingo for a knock-out.

1295
01:14:32,940 --> 01:14:35,035
Both genes for prestin are gone.

1296
01:14:38,030 --> 01:14:41,160
This trace is the plus plus,
the wild type, or normal.

1297
01:14:42,640 --> 01:14:45,980
And there's big changes
in outer hair cells

1298
01:14:45,980 --> 01:14:48,455
when you depolarize
and hyperpolarize them.

1299
01:14:48,455 --> 01:14:52,350
And these big changes are on
the order of half a micrometer.

1300
01:14:52,350 --> 01:14:53,650
So this is a length axis.

1301
01:14:55,690 --> 01:14:57,960
In the knock-out,
the outer hair cells

1302
01:14:57,960 --> 01:14:59,739
don't change length
at all when they're

1303
01:14:59,739 --> 01:15:01,030
depolarized and hyperpolarized.

1304
01:15:02,220 --> 01:15:06,710
In the heterozygote,
which is the case when

1305
01:15:06,710 --> 01:15:08,815
you have one gene
intact for prestin

1306
01:15:08,815 --> 01:15:10,370
and the other gene
is knocked out,

1307
01:15:10,370 --> 01:15:11,536
it's an intermediate result.

1308
01:15:15,310 --> 01:15:17,150
OK, so the outer
hair cell motility

1309
01:15:17,150 --> 01:15:20,740
is knocked out by knocking
out this one protein.

1310
01:15:20,740 --> 01:15:22,610
So that's pretty good
evidence that it's

1311
01:15:22,610 --> 01:15:24,130
involved in the
cochlear amplifier.

1312
01:15:26,410 --> 01:15:27,600
What else was measured?

1313
01:15:27,600 --> 01:15:33,630
Well, they wanted to
measure hearing sensitivity.

1314
01:15:33,630 --> 01:15:36,960
And so in humans,
what you might do

1315
01:15:36,960 --> 01:15:39,894
for that is put a subject in
a soundproof chamber and say,

1316
01:15:39,894 --> 01:15:41,560
raise your hand when
you hear the sound.

1317
01:15:41,560 --> 01:15:45,000
But you could do that in
mice, but it takes a long time

1318
01:15:45,000 --> 01:15:48,690
to train mice or other
experimental animals

1319
01:15:48,690 --> 01:15:50,180
to do those behavioral tests.

1320
01:15:50,180 --> 01:15:52,820
So they did an electro
physiological test.

1321
01:15:54,080 --> 01:15:57,440
They measured what's called
the auditory brain stem

1322
01:15:57,440 --> 01:15:59,670
response, so the ABR.

1323
01:16:06,720 --> 01:16:15,998
This stands for auditory
brain stem response.

1324
01:16:19,940 --> 01:16:20,890
OK.

1325
01:16:20,890 --> 01:16:29,330
And that top right graph gives
you the ABR threshold in dB.

1326
01:16:29,330 --> 01:16:31,510
So something that has
a really low threshold

1327
01:16:31,510 --> 01:16:33,315
is a really good hearing animal.

1328
01:16:34,680 --> 01:16:37,510
This is the wild type
and the heterozygote.

1329
01:16:39,700 --> 01:16:42,560
And something that has
a very high threshold

1330
01:16:42,560 --> 01:16:44,580
means you really had
to crank up the sound

1331
01:16:44,580 --> 01:16:47,580
to get any kind
of response at all

1332
01:16:47,580 --> 01:16:50,000
as you see in the open
symbols for the knock-out.

1333
01:16:50,000 --> 01:16:51,870
So how do they measure that ABR?

1334
01:16:51,870 --> 01:16:55,030
You could do it in animals
or humans as a clinical test.

1335
01:16:55,030 --> 01:16:57,210
Put electrodes on the
surface of the skin.

1336
01:16:59,290 --> 01:17:02,930
You turn on a click
or a tone burst.

1337
01:17:02,930 --> 01:17:04,439
In this case, they
used tone bursts

1338
01:17:04,439 --> 01:17:05,480
of different frequencies.

1339
01:17:07,900 --> 01:17:11,130
And you can imagine that the
auditory brain stem is way down

1340
01:17:11,130 --> 01:17:13,640
in the head, and you're
measuring on the surface.

1341
01:17:13,640 --> 01:17:15,490
So you've got a
click, click, click.

1342
01:17:15,490 --> 01:17:18,040
And you measure
thousands of responses.

1343
01:17:18,040 --> 01:17:19,850
So there's a lot of noise.

1344
01:17:19,850 --> 01:17:21,010
There's noise in the room.

1345
01:17:21,010 --> 01:17:23,730
There's noise from other
neurons in the brain.

1346
01:17:23,730 --> 01:17:26,560
But eventually, after
thousands of averages,

1347
01:17:26,560 --> 01:17:28,950
that little tiny signal
comes out of the noise,

1348
01:17:28,950 --> 01:17:33,350
and you get a response if the
brain stem is responding--

1349
01:17:33,350 --> 01:17:35,320
that is, if the hair
cells are responding,

1350
01:17:35,320 --> 01:17:38,380
the nerve fibers send
messages into the brain stem,

1351
01:17:38,380 --> 01:17:40,220
and the brain stem
finally responds.

1352
01:17:40,220 --> 01:17:42,340
It's a very good test
of auditory sensitivity.

1353
01:17:43,470 --> 01:17:44,950
And what does it show?

1354
01:17:44,950 --> 01:17:47,960
It shows that without prestin
in the knock-out animal,

1355
01:17:47,960 --> 01:17:50,530
you have a huge hearing loss.

1356
01:17:50,530 --> 01:17:51,840
How big is the hearing loss?

1357
01:17:51,840 --> 01:17:55,850
Well, looks like it's
about 40 to 60 dB.

1358
01:17:58,120 --> 01:18:00,440
So when you have
prestin knocked out,

1359
01:18:00,440 --> 01:18:09,870
you have a hearing
loss of 40 to 60 dB.

1360
01:18:13,630 --> 01:18:17,130
How much amplification does the
cochlear amplifier give you?

1361
01:18:17,130 --> 01:18:18,705
40 to 60 dB.

1362
01:18:20,140 --> 01:18:22,980
You're not completely
deaf without it,

1363
01:18:22,980 --> 01:18:24,725
but you have a
severe hearing loss.

1364
01:18:26,020 --> 01:18:28,290
Most of you would not
be able to understand

1365
01:18:28,290 --> 01:18:30,710
what I'm saying with
a 60 dB hearing loss,

1366
01:18:30,710 --> 01:18:33,750
unless you were sitting
right up here in the front.

1367
01:18:37,990 --> 01:18:40,960
What else do I want to
say about this paper?

1368
01:18:40,960 --> 01:18:42,480
Not too much.

1369
01:18:42,480 --> 01:18:43,900
There are some problems with it.

1370
01:18:43,900 --> 01:18:46,050
Any paper has problems.

1371
01:18:46,050 --> 01:18:47,660
They found that,
for some reason,

1372
01:18:47,660 --> 01:18:52,440
all the hair cells were lost
for the high frequency basal

1373
01:18:52,440 --> 01:18:53,275
part of the cochlea.

1374
01:18:54,680 --> 01:18:57,790
It's just a problem in
some strains of mice

1375
01:18:57,790 --> 01:19:01,830
that they lose hair cells in
a certain part of the cochlea.

1376
01:19:01,830 --> 01:19:05,360
So within these gray bars,
you can't conclude anything.

1377
01:19:07,260 --> 01:19:09,720
Now, they looked
at the hair cells.

1378
01:19:09,720 --> 01:19:11,640
They just took them
out and looked at them

1379
01:19:11,640 --> 01:19:13,170
in the microscope.

1380
01:19:13,170 --> 01:19:15,000
And they said, wow,
in the knock-out,

1381
01:19:15,000 --> 01:19:17,730
the hair cells are
actually smaller.

1382
01:19:17,730 --> 01:19:22,850
Well, you cut out all this
protein from the membrane

1383
01:19:22,850 --> 01:19:24,847
in the knock-out, right?

1384
01:19:24,847 --> 01:19:27,055
So if there's a lot less
membrane there, they shrink.

1385
01:19:29,870 --> 01:19:32,350
The outer hair cell membrane
is packed with prestin.

1386
01:19:32,350 --> 01:19:35,630
So you could argue, oh, all
the hair cells are shorter,

1387
01:19:35,630 --> 01:19:37,780
and so they're not
working the same way.

1388
01:19:37,780 --> 01:19:39,250
Every paper has its problems.

1389
01:19:39,250 --> 01:19:41,700
but that's what
these graphs mean.

1390
01:19:41,700 --> 01:19:43,390
The hair cells at
rest are actually

1391
01:19:43,390 --> 01:19:45,400
shorter in the knock-out.

1392
01:19:45,400 --> 01:19:48,360
So just some caveats.

1393
01:19:48,360 --> 01:19:51,190
I think the main
message is prestin

1394
01:19:51,190 --> 01:19:53,655
is essential for the
cochlear amplifier.

1395
01:19:55,040 --> 01:19:59,630
And without it, you have a
big hearing loss, 40 to 60 dB.

1396
01:20:01,020 --> 01:20:03,610
Now, one of the other
things they measured in here

1397
01:20:03,610 --> 01:20:06,570
is something called
the distortion product

1398
01:20:06,570 --> 01:20:07,450
otoacoustic emission.

1399
01:20:08,700 --> 01:20:13,040
And let me just, as the last
thing in today's lecture,

1400
01:20:13,040 --> 01:20:15,990
tell you about what an
otoacoustic emission is.

1401
01:20:15,990 --> 01:20:19,630
These were discovered about the
same time as outer hair cell

1402
01:20:19,630 --> 01:20:23,310
electromotility by
David Kemp, who's

1403
01:20:23,310 --> 01:20:24,600
at University College London.

1404
01:20:25,640 --> 01:20:29,930
And he was doing some kind
of hearing tests in people,

1405
01:20:29,930 --> 01:20:34,410
and he developed a very,
very sensitive microphone

1406
01:20:34,410 --> 01:20:37,095
that had a very low
electrical noise.

1407
01:20:38,290 --> 01:20:40,355
He stuck that microphone
in an ear canal.

1408
01:20:41,710 --> 01:20:43,060
And what did he find?

1409
01:20:43,060 --> 01:20:47,070
The microphone actually picked
up sound in the ear canal.

1410
01:20:48,340 --> 01:20:49,544
Oh my gosh, this is crazy.

1411
01:20:49,544 --> 01:20:51,835
There's not supposed to be
sound coming out of the ear,

1412
01:20:51,835 --> 01:20:54,870
you're supposed to be putting
sound into the ear, right?

1413
01:20:54,870 --> 01:20:59,630
So he named it
otoacoustic emission.

1414
01:20:59,630 --> 01:21:01,680
OK, "oto" means ear.

1415
01:21:03,150 --> 01:21:07,880
"Acoustic" means sound, and
"emissions" means coming out,

1416
01:21:07,880 --> 01:21:10,410
sound coming out of the ear.

1417
01:21:10,410 --> 01:21:12,990
This was an amazing
discovery, and it

1418
01:21:12,990 --> 01:21:16,440
fits very nicely with
the idea that there's

1419
01:21:16,440 --> 01:21:19,850
something in the ear
that's actually moving,

1420
01:21:19,850 --> 01:21:21,330
that being the outer hair cells.

1421
01:21:23,020 --> 01:21:26,510
The outer hair cells are
moving either spontaneously--

1422
01:21:26,510 --> 01:21:29,250
and there are some otoacoustic
emissions that are spontaneous.

1423
01:21:30,440 --> 01:21:33,640
About half of us have
spontaneous otoacoustic

1424
01:21:33,640 --> 01:21:35,260
emissions in our ears.

1425
01:21:35,260 --> 01:21:38,730
Now, before you get too excited
and go home and listen to them,

1426
01:21:38,730 --> 01:21:41,340
they are very, very
low levels of sound.

1427
01:21:41,340 --> 01:21:45,590
Most of them are below
the audio metric hearing

1428
01:21:45,590 --> 01:21:46,990
curve for human hearing.

1429
01:21:46,990 --> 01:21:49,460
So you really, in
most cases, are not

1430
01:21:49,460 --> 01:21:52,010
aware of your
otoacoustic emissions.

1431
01:21:52,010 --> 01:21:56,220
This is very different from
the sensation that some of us

1432
01:21:56,220 --> 01:22:01,050
have of ringing in
the ears, tinnitus.

1433
01:22:13,040 --> 01:22:14,340
Does anybody have tinnitus?

1434
01:22:14,340 --> 01:22:16,380
I have tinnitus,
especially my left ear.

1435
01:22:16,380 --> 01:22:19,960
If I close my left ear, often
I can hear kind of a noise.

1436
01:22:19,960 --> 01:22:21,510
Put my head on the
pillow at night,

1437
01:22:21,510 --> 01:22:23,390
I can hear a little
noise in there.

1438
01:22:23,390 --> 01:22:26,830
So that's a sensation
that I have even

1439
01:22:26,830 --> 01:22:28,590
though there's no
sound going in my ear,

1440
01:22:28,590 --> 01:22:30,400
and it's not an
otoacoustic emission.

1441
01:22:30,400 --> 01:22:32,025
You could put a
microphone in that ear,

1442
01:22:32,025 --> 01:22:33,800
and there is no sound there.

1443
01:22:33,800 --> 01:22:38,035
Something in my brain is telling
me that I am hearing a sound.

1444
01:22:39,460 --> 01:22:42,000
Some people are very
disturbed by tinnitus.

1445
01:22:42,000 --> 01:22:44,250
There's no good
treatment for it.

1446
01:22:44,250 --> 01:22:46,150
Historically, the
famous treatment

1447
01:22:46,150 --> 01:22:50,030
was by an ear surgeon who said,
OK, I'll cure your tinnitus.

1448
01:22:50,030 --> 01:22:54,260
And he took out the person's
ear, the cochlea was taken out.

1449
01:22:54,260 --> 01:22:56,700
Tinnitus didn't change one bit.

1450
01:22:56,700 --> 01:22:59,190
Maybe it's like phantom
limb pain, something

1451
01:22:59,190 --> 01:23:00,930
to do with your
central nervous system.

1452
01:23:02,020 --> 01:23:04,110
Tinnitus and
otoacoustic emissions

1453
01:23:04,110 --> 01:23:05,240
are completely different.

1454
01:23:05,240 --> 01:23:09,250
Otoacoustic emissions are
associated with normal hearing,

1455
01:23:09,250 --> 01:23:11,650
normal outer hair cell function.

1456
01:23:11,650 --> 01:23:14,360
They're sometimes used
as a clinical test

1457
01:23:14,360 --> 01:23:17,900
for hearing in patients
who can't raise their arm.

1458
01:23:17,900 --> 01:23:20,770
For example, most states,
like Massachusetts,

1459
01:23:20,770 --> 01:23:25,330
you have to, by law, test
newborns for good hearing.

1460
01:23:25,330 --> 01:23:28,240
An otoacoustic
emission test is one.

1461
01:23:28,240 --> 01:23:31,760
So how does that work if only
50% of the people have them?

1462
01:23:31,760 --> 01:23:34,770
Well, there are other types
of otoacoustic emissions

1463
01:23:34,770 --> 01:23:38,990
that are evoked-- that
is, you put sound in,

1464
01:23:38,990 --> 01:23:42,490
and you listen for the
sound coming back out.

1465
01:23:42,490 --> 01:23:44,460
Some of these are
transiently evoked.

1466
01:23:44,460 --> 01:23:48,320
You put a click in, and a
few milliseconds later you

1467
01:23:48,320 --> 01:23:50,890
get a sound coming back out.

1468
01:23:50,890 --> 01:23:54,060
And that's the
usual clinical test.

1469
01:23:54,060 --> 01:23:57,000
And 100% of normal
hearing humans

1470
01:23:57,000 --> 01:23:59,930
have these so-called
otoacoustic emissions.

1471
01:23:59,930 --> 01:24:03,230
Now, what would be
an indication if you

1472
01:24:03,230 --> 01:24:06,480
had a patient with no
otoacoustic emissions?

1473
01:24:06,480 --> 01:24:11,380
Well, it is a good test
of whether your middle ear

1474
01:24:11,380 --> 01:24:15,025
and inner ear is working
as far along the pathway

1475
01:24:15,025 --> 01:24:16,190
as the outer hair cells.

1476
01:24:17,300 --> 01:24:20,790
Beyond that, it doesn't test.

1477
01:24:20,790 --> 01:24:24,865
It just tests up to
the electromotile part

1478
01:24:24,865 --> 01:24:25,740
of the hearing organ.

1479
01:24:25,740 --> 01:24:27,490
So it doesn't test
the inner hair cells.

1480
01:24:27,490 --> 01:24:29,239
It doesn't test the
auditory nerve fibers.

1481
01:24:30,180 --> 01:24:34,830
But much of hearing problem
arises in the outer hair cells,

1482
01:24:34,830 --> 01:24:36,510
so it's a pretty
good first step.

1483
01:24:36,510 --> 01:24:38,980
It's a very easy test to do.

1484
01:24:38,980 --> 01:24:42,685
And I think when we have the
lab tour over at the Mass Eye

1485
01:24:42,685 --> 01:24:44,560
and Ear Infirmary at
the end of the semester,

1486
01:24:44,560 --> 01:24:48,190
we'll be seeing some
otoacoustic emissions recorded

1487
01:24:48,190 --> 01:24:48,860
from a human.

1488
01:24:48,860 --> 01:24:51,130
There's a project
going on there now.

1489
01:24:51,130 --> 01:24:53,156
So we'll have a demo of that.

1490
01:24:55,290 --> 01:24:59,910
OK, so if there
aren't any questions,

1491
01:24:59,910 --> 01:25:03,540
we'll meet up again on Monday.