Harvard-MIT Division of Health Sciences and Technology
HST.722J: Brain Mechanisms for Hearing and Speech
Course Instructor: Kenneth E. Hancock
HST.722 Brain Mechanisms of Speech and Hearing
Fall 2005
Dorsal Cochlear Nucleus
September 14, 2005
Ken Hancock
Dorsal Cochlear Nucleus (DCN)
•
•
•
•
Overview of the cochlear nucleus and its subdivisions
Anatomy of the DCN
Physiology of the DCN
Functional considerations
Dorsal Cochlear Nucleus (DCN)
•
•
•
•
Overview of the cochlear nucleus and its subdivisions
Anatomy of the DCN
Physiology of the DCN
Functional considerations
The cochlear nucleus
DCN
VCN
AN
AN fibers terminate in a “tonotopic” or “cochleotopic” pattern
1 mm
DCN
36.0
kHz
36.0 kHz
I
III
II
10.2
kHz
10.2 kHz
AVCN
2.7
kHz
2.7 kHz
PVCN
ANR
0.17
0.17 kHz
kHz
sg
b
Figure by MIT OCW.
Major subdivisions of the cochlear nucleus
N
DC
AVCN
AA
AP
PD
OA
MA
Spherical bushy
VE
ST
PV
NE
RV
E
PV
AU
CN
D IT
NE ORY
RV
E
Globular bushy
Figure by MIT OCW.
Multipolar
Octopus
Summary of pathways originating in the cochlear nucleus
Inferior colliculus
Midline
Lateral lemniscus
N
DC
AVCN
AA
SBC
AP
OA
GBC
MA VCN
PD
OA
MA
VE
ST
Superior olive
PV
NE
RV
E
P
AU
DIT
NE ORY
RV
E
Figure by MIT OCW.
Projections suggest DCN is a different animal than VCN
Inferior colliculus
Midline
Lateral lemniscus
N
DC
AVCN
AA
SBC
AP
OA
GBC
MA VCN
PD
OA
MA
VE
ST
Superior olive
PV
NE
RV
E
P
AU
D IT
NE ORY
RV
E
Figure by MIT OCW.
• (All roads lead to the inferior colliculus)
• VCN projects directly to structures dealing with binaural
hearing and olivocochlear feedback
• DCN ???
Dorsal Cochlear Nucleus
• Overview of the cochlear nucleus and its subdivisions
– DCN projections do not reveal its function
• Anatomy of the DCN
• Physiology of the DCN
• Functional considerations
Dorsal Cochlear Nucleus
• Overview of the cochlear nucleus and its subdivisions
– DCN projections do not reveal its function
• Anatomy of the DCN
• Physiology of the DCN
• Functional considerations
4
200
s
ulo
o
p
o
oun
N
DC
golgi
cartwheel
granule
Tz
Kanold Young
2001
Somatosensory
Auditory
Vestibular
stellate
?
?
I.C.
vertical
fusiform
giant
D
T
auditory
nerve
PVCN
Figure by MIT OCW.
Dorsal Cochlear Nucleus
• Overview of the cochlear nucleus and its subdivisions
– DCN projections do not reveal its function
• Anatomy of the DCN
– more complex than other CN subdivisions
– nonauditory inputs
– similar organization to cerebellar cortex
• Physiology of the DCN
• Functional considerations
Dorsal Cochlear Nucleus
• Overview of the cochlear nucleus and its subdivisions
– DCN projections do not reveal its function
• Anatomy of the DCN
– more complex than other CN subdivisions
– nonauditory inputs
– similar organization to cerebellar cortex
• Physiology of the DCN
• Functional considerations
Photograph of Eric Young
removed due to copyright reasons.
Please see:
http://www.bme.jhu.edu/labs/chb/
people/index.php?page=ABOUT
&user=eyoung
Eric Young
Response Map classification scheme
~ Auditory Nerve
increasing inhibition
Type II
Type III
Type IV
Type V
Sound Level
Type I
Discharge Rate
FREQUENCY
600
300
400
200
200
100
0
0
FREQUENCY
200
150
100
100
50
0
0
10 dB
Sound Level
200
100
0
Sound Level
BF Tone
Excitatory
Responses
Noise
Inhibitory
Responses
Figures by MIT OCW.
Spont.Act
10 dB
DCN: Vertical cells are type II and type III units
type II
BF
type III
dB atten
-20
-50
-80
-90
400
0
0.5
-95
1
2
5
10
20
Rate
-70
300
200
100
BF tone
noise
300
0
1.25
2
5
10
200
Rate
-40
-60
20
30
40
50
60
70
80
90
100
Rate, Spikes/s
Rate, Spikes/s
-30
100
0
Sound Level
20
Frequency, kHz
0
Sound Level
Frequency, kHz
Figures by MIT OCW.
•Narrow V-shaped region of excitation
•No spontaneous activity
•Tone response >> noise response
•V-shaped region of excitation
•Inhibitory sidebands
Evidence: Antidromic stimulation (Young 1980)
Antidromic stimulation
•record from neuron
•shock its axon
recording
electrode
recording
electrode
DCN
fusiform
stimulating
electrode
vertical
DAS
giant
VCN
stimulating electrode
Figures by MIT OCW.
DCN: “Principal” cells are type III and type IV units
TYPE III
30
40
50
60
70
80
90
300
0
1.25
200
Rate
Rate, spikes/s
20
100
0
Sound Level
100
2
5
10
20
Frequency, kHz
TYPE IV
dB attn
25
Rate, spikes/s
35
45
150
65
75
85
95
400
0
5
10
20
Rate
55
100
Spont
50
0
Sound Level
50
Frequency, kHz
•“Island of excitation” & “Sea of inhibition”
•BF rate-level curve inhibited at high levels
•Noise rate-level curve ~ monotonic
Evidence:
Antidromic stimulation (Young 1980)
Intracellular recording and labeling (Rhode et al.
1983, Ding et al. 1996)
Figures by MIT OCW.
Neural circuitry underlying DCN physiology:
type II units inhibit type IV units
TYPE II
BF
dB attn.
-20
Rate, spikes/s
-30
300
Rate
-40
-50
200
-60
100
-70
0
BF tone
noise
Sound level
-80
-90
400
0
0.5
-95
1
2
5
10
20
"Reciprocal" responses
Frequency, kHz
TYPE IV
dB attn.
Vertical
25
Rate, spikes/s
35
Fusiform
150
55
65
75
85
95
400
0
5
10
20
Rate
45
100
Spont
50
0
Sound level
50
Giant
Frequency, kHz
Figures by MIT OCW.
Classic experiment: type II units inhibit type IV units
• multiunit recording Voigt & Young (1980, 1990)
Cross-correlogram
Cross-correlogram
30 type IV firing rate
given type II fires at
20
t=0
Spikes/Second
10
-10
-20
-10
-5
0
Milliseconds
inhibitory
trough
5
10
type II unit
type IV unit
300
200
BF Tone
Rate, Spikes
Rate, Spikes
400
200
Noise
100
0
110
60
BBN
100
BF
0
-25
10
Level, dB Attn
25
Level,dB
Figures by MIT OCW.
75
DCN physiology so far…
IV
~ principal cells
+
II
~ vertical cells
auditory nerve
+
• type II units inhibit type IV units
• BUT this analysis based on pure-tone responses
⇒ what happens with more general stimuli???
Inhibition from type II units doesn’t account for everything
spectrum level
dB attn
10
200
Rate (spikes/sec)
20
30
20 dB
Notch noise stimuli
Type IV unit response map
40
50
Rate (spikes/sec)
200
60
Upper Inhibitory Sideband 70
80
0.5
1
5
10
Frequency (kHz)
40
Spont.
Data
100
Model
0
0.5
1
Frequency (kHz)
10
Figure by MIT OCW.
• (DCN responses to broadband stimuli cannot be predicted from
responses to tones: nonlinear)
• Type II units do not respond to notch noise—whither the inhibition?
• Response map has two inhibitory regions?
40
DCN notch noise sensitivity due to wideband inhibition
IV
Broadband noise
Excitatory
Notch noise
WBI
Inhibitory
Frequency
level
Figure by MIT OCW.
• strong AN input dominates
AN input
to type IV
unit
• type IV response is excitatory
level
• type IV loses greater portion
of its excitatory input
• WBI input dominates
AN input
to WBI
• type IV response is inhibitory
frequency
frequency
Nelken & Young 1994
5
-5
-15
-25
-35
-45
-55
-65
-75
-85
-95
-105
• broadly-tuned, onset-chopper
units are found in the PVCN
(Winter & Palmer 1995)
500
Rate, spikes/s
Relative tone level (dB)
PVCN: is the D-stellate cell the wideband inhibitor?
400
Noise
300
1000
200
0
0
100
1000
0
10
20
100
BF tone
50
Level, dB attn
0
• typically respond better to
broadband noise than to tones
5000 10000
Frequency (Hz)
Figure by MIT OCW.
• such responses arise from
radiate or stellate neurons (Smith
& Rhode 1989)
DCN
PVCN
a
• stellate cells send axons dorsally
into the DCN, thus called “Dstellate cells” (Oertel et al. 1990)
• D-stellate cells are inhibitory
(Doucet & Ryugo 1997)
Figure by MIT OCW.
Summary: Circuitry of DCN deep layer
Type II inhibitory inputs (strong)
Sound level
UIS from ? source (weak)
Inhibitory
Excitatory input
AN fibers?
Excitatory
Spirou and Young 1991
Frequency
IV
type II
type II
300
BF Tone
Excitatory
Inhibitory
200
Noise
100
Best frequency
0
110
60
Level, dB attn
W.B.I.
500
W.B.I.
Rate, spikes/s
Rate, spike/s
400
Noise
400
300
1000
200
100
0
10
100
“reciprocal” response
properties
Figures by MIT OCW.
0
0
10
20
BF tone
50
Level, dB attn
0
Summary of DCN anatomy and physiology
granule
Nonauditory
Somatosensory
Auditory
Vestibular
• vertical cell
• type II unit
• narrowband
inhibition
fusiform
D
• D-stellate cell
• onset-chopper
• wideband
inhibition
Dorsal Cochlear Nucleus
• Overview of the cochlear nucleus and its subdivisions
– DCN projections do not reveal its function
• Anatomy of the DCN
– more complex than other CN subdivisions
– nonauditory inputs
– similar organization to cerebellar cortex
• Physiology of the DCN
– diverse response properties
– complex interconnections
– highly nonlinear
• Functional considerations
Dorsal Cochlear Nucleus
• Overview of the cochlear nucleus and its subdivisions
– DCN projections do not reveal its function
• Anatomy of the DCN
– more complex than other CN subdivisions
– nonauditory inputs
– similar organization to cerebellar cortex
• Physiology of the DCN
– diverse response properties
– complex interconnections
– highly nonlinear
• Functional considerations
Filtering by the pinna provides cues
to sound source location
“Head Related Transfer Function ” (HRTF)
A
60
Transformation (dB)
Outer ear gain
10
.
-15
.
+15°
5
0
90
-5
-15
0°
.
.
-10
15
-15°
.
-15
Human
0
-20
2
3
5
.
7
10
15
20
Frequency (kHz)
“first notch” frequency changes with elevation
Figures by MIT OCW.
Type IV units are sensitive to HRTF first notch
• type IV units are inhibited by
notches centered on BF
El = 30o, Az = -15o
Rate / spikes per second
Gain / dB
30 El = 30o, Az = 15o
20
10
0
-10
30
20
10
0
-10
-15dB
-35 dB
-55 dB
-75 dB
300
-95 dB
3
5
10
30
Frequency / kHz
Rate / spikes per second
• null in DCN population response
may code for sound source
location
200
Reiss & Young
2005
Behavior ⇒
May 2000
El = 30o, Az = -15o
El = 30o,
o
Az = 15
100
spont.
0
Physiology
⇒
3
5
10
Stimulus notch frequency
Figures by MIT OCW.
30
Dorsal Cochlear Nucleus
• Overview of the cochlear nucleus and its subdivisions
– DCN projections do not reveal its function
• Anatomy of the DCN
– more complex than other CN subdivisions
– receives nonauditory inputs
– has similar organization to cerebellar cortex
• Physiology of the DCN
– diverse response properties
– complex interconnections
– highly nonlinear
• Functional considerations
– coding sound source location based on pinna cues
DCN is a “cerebellum-like structure”
Generic cerebellum-like structure
Predictive Inputs :
descending
auditory
Corollary discharge signals
Higher levels of the same modality
Other sensory modalities (e.g. proprioception)
?
Granule layer
somatosensory
Molecular layer
“plastic”
synapses
Principal cell layer
Sensory input layer
Input from a sensory surface
cochlea
Figure by MIT OCW.
Synaptic plasticity: Long-Term Potentiation (LTP)
Tzounopoulos 2004
• “Classical” LTP demonstration at the hippocampal CA3-CA1 synapse
• LTP evoked by tetanic stimulation (mechanism involves NMDA receptors)
Electric fish provide clues to cerebellum-like function
black ghost knifefish
(Apteronotus albifrons)
Photograph removed due to copyright reasons.
Please see the Nelson Lab home page:
http://nelson.beckman.uiuc.edu
electric organ
discharge
(EOD)
• electrical activity detected by electric lateral line
• afferent activity transmitted to electric lateral line
lobe (ELL), analogous to DCN
Electric fields provide information about nearby objects
Figures by MIT OCW.
• BUT the fish generates its own electric fields:
• tail movements
• ventilation
⇒ cerebellum-like ELL helps solve this problem
Bell 2001
What do cerebellum-like structures do???
• Subtract the expected input pattern from the actual input
pattern to reveal unexpected or novel features of a stimulus.
– DCN: pinna movement is expected to shift the first notch,
independent of what the sound source is doing
Dorsal Cochlear Nucleus
• Overview of the cochlear nucleus and its subdivisions
– DCN projections do not reveal its function
• Anatomy of the DCN
– more complex than other CN subdivisions
– nonauditory inputs
– similar organization to cerebellar cortex
• Physiology of the DCN
– diverse response properties
– complex interconnections
– highly nonlinear
• Functional considerations: the DCN may…
– code sound source location based on pinna cues
– extract novel components of response
DCN may play a role in tinnitus
This makes
no sense!
• percept of noise, ringing, buzzing, etc.
• affects up to 80% of the population
• 1 in 200 are debilitated
• (not voices in the head)
So why DCN? Because tinnitus…
• involves plasticity
• may involve somatosensory effects
Levine 1999
Dorsal Cochlear Nucleus
• Overview of the cochlear nucleus and its subdivisions
– DCN projections do not reveal its function
• Anatomy of the DCN
– more complex than other CN subdivisions
– nonauditory inputs
– similar organization to cerebellar cortex
• Physiology of the DCN
– diverse response properties
– complex interconnections
– highly nonlinear
• Functional considerations: the DCN may…
– code sound source location based on pinna cues
– extract novel components of response
– contribute to tinnitus
Selected References
Slide 5:
Ryugo DK, May SK (1993) The projections of intracellularly labeled auditory nerve fibers to the dorsal
cochlear nucleus of cats. J Comp Neurol 329:20-35.
Slide 6:
Ehret G, Romand R, eds (1997) The Central Auditory System. New York: Oxford University
Press.
Slide 7:
Ehret G, Romand R, eds (1997) The Central Auditory System. New York: Oxford University
Press.
Slide 12:
Lorente de Nó R (1981) The Primary Acoustic Nuclei. New York: Raven.
Kane ES, Puglisi SG, Gordon BS (1981) Neuronal types in the deep dorsal cochlear nucleus of the cat. I.
Giant neurons. J Comp Neurol 198:483-513.
Slide 15:
Young ED (1984) Response characteristics of neurons of the cochlear nuclei. In: Hearing Science (Berlin
CI, ed), pp 423-460. San Diego: College-Hill. ISBN: 0316091693.
Slides 16, 18, 19:
Young ED (1984) Response characteristics of neurons of the cochlear nuclei. In: Hearing Science (Berlin
CI, ed), pp 423-460. San Diego: College-Hill.
Young ED, Davis KA (2001) Circuitry and Function of the Dorsal Cochlear Nucleus. In: Integrative
Functions in the Mammalian Auditory Pathway (Oertel D, Popper AN, Fay RR, eds). New York: SpringerVerlag.
Selected References, continued
Slide 20:
VOIGT, H. F. AND YOUNG, E. D. Cross-correlation analysis of inhibitory interactions in dorsal cochlear
nucleus. J. Neurophysiol. 64: 1590- 16 10, 1990.
Young ED, Davis KA (2001) Circuitry and Function of the Dorsal Cochlear Nucleus. In: Integrative Functions
in the Mammalian Auditory Pathway (Oertel D, Popper AN, Fay RR, eds). New York: Springer-Verlag.
Slide 22:
Spirou GA, Young ED (1991) Organization of dorsal cochlear nucleus type IV unit response maps and their
relationship to activation by band-limited noise. J Neurophysiol 66:1750-1768.
Slide 23:
Nelken I, Young ED (1994) Two separate inhibitory mechanisms shape the responses of dorsal cochlear
nucleus type IV units to narrowband and wideband stimuli. J Neurophysiol 71:2446-2462.
Slide 24:
Winter IM, Palmer AR (1995) Level dependence of cochlear nucleus onset unit responses and facilitation by
second tones or broadband noise. J Neurophysiol 73:141-159.
Young ED, Davis KA (2001) Circuitry and Function of the Dorsal Cochlear Nucleus. In: Integrative Functions
in the Mammalian Auditory Pathway (Oertel D, Popper AN, Fay RR, eds). New York: Springer-Verlag.
Oertel D, Wu SH, Garb MW, Dizack C (1990) Morphology and physiology of cells in slice preparations of the
posteroventral cochlear nucleus of mice. J Comp Neurology 295:136-154.
Selected References, continued
Slide 25:
Spirou GA, Young ED (1991) Organization of dorsal cochlear nucleus type IV unit response maps and their
relationship to activation by band-limited noise. J Neurophysiol 66:1750-1768.
Nelken I, Young ED (1994) Two separate inhibitory mechanisms shape the responses of dorsal cochlear
nucleus type IV units to narrowband and wideband stimuli. J Neurophysiol 71:2446-2462.
Young ED, Davis KA (2001) Circuitry and Function of the Dorsal Cochlear Nucleus. In: Integrative Functions
in the Mammalian Auditory Pathway (Oertel D, Popper AN, Fay RR, eds). New York: Springer-Verlag.
Slide 26:
Oertel D, Wu SH, Garb MW, Dizack C (1990) Morphology and physiology of cells in slice preparations of the
posteroventral cochlear nucleus of mice. J Comp Neurology 295:136-154.
Slide 29:
Geisler CD (1998) From Sound to Synapse: Physiology of the Mammalian Ear.: Oxford University Press.
Slide 30:
Young ED, Spirou GA, Rice JJ, Voigt HF (1992) Neural organization and responses to complex stimuli in the
dorsal cochlear nucleus. Philos Trans R Soc Lond B Biol Sci 336:407-413.
Slide 32:
Bell CC (2001) Memory-based expectations in electrosensory systems. Curr Opin Neurobiol 11:481-487.
Slide 35:
Zakon HH (2003) Insight into the mechanisms of neuronal processing from electric fish. Curr Opin Neurobiol
13:744-750.