HST.722 Brain Mechanisms of Speech and Hearing … Brain Mechanisms for Hearing and Speech Course Instructor: ... • Physiology of the DCN – diverse response properties – complex

Harvard-MIT Division of Health Sciences and TechnologyHST.722J: Brain Mechanisms for Hearing and SpeechCourse Instructor: Kenneth E. Hancock

HST.722 Brain Mechanisms of Speech and HearingFall 2005

Dorsal Cochlear NucleusSeptember 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

I

IIIII

0.17 kHz

2.7 kHz

10.2 kHz

36.0 kHz

ANR

sgb

1 mm

DCN

AVCN

PVCN

36.0 kHz

10.2 kHz

2.7 kHz

0.17 kHz

Figure by MIT OCW.

Major subdivisions of the cochlear nucleus

PVCN

AVCNDCN

OAPD

AP

PV

MA

AA

VEST NERVE

AUDITORYNERVE

Spherical bushy

Globular bushy Multipolar

Octopus

Spherical bushy

Globular bushy Multipolar

Octopus

Figure by MIT OCW.

Summary of pathways originating in the cochlear nucleus

PVCN

AVCN

DCN

OAPD

AP

PV

MA

AA

VEST NERVE

AUDITORYNERVE

Midline

SBC

GBC MAOA

SBC

GBC MAOA

Inferior colliculus

Lateral lemniscus

Superior olive

Figure by MIT OCW.

Projections suggest DCN is a different animal than VCN

• (All roads lead to the inferior colliculus)• VCN projects directly to structures dealing with binaural

hearing and olivocochlear feedback• DCN ???

PVCN

AVCN

DCN

OAPD

AP

PV

MA

AA

VEST NERVE

AUDITORYNERVE

Midline

SBC

GBC MAOA

SBC

GBC MAOA

Inferior colliculus

Lateral lemniscus

Superior olive

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• Physiology of the DCN• Functional considerations



• Anatomy of the DCN• Physiology of the DCN• Functional considerations

DCN

PVCN

I.C.I.C.

SomatosensoryAuditory

Vestibular


Vestibular


Vestibular

TD

?

?

TD

?

D

?

?

granulegranule

giant

fusiform

giant

fusiform

auditory nerve

auditory nerve

golgi

cartwheel

golgi

cartwheel

stellategolgi

cartwheel

verticalvertical

Kanold Young2001

Tzounopoulos 2004

Figure by MIT OCW.



• Anatomy of the DCN– more complex than other CN subdivisions– nonauditory inputs– similar organization to cerebellar cortex

• Physiology of the DCN• Functional considerations




• 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

200

10050

100

150

100

200

100

200

300

200

400

0 0

600

0 0 0

FREQUENCY FREQUENCY

Type I Type II Type III Type IV Type V

Sound Level Sound Level 10 dB10 dB

Soun

d Le

vel

Dis

char

ge R

ate

Excitatory Responses

Inhibitory Responses

BF Tone

Noise

Spont.Act

Figures by MIT OCW.

DCN: Vertical cells are type II and type III units

•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)

BF tonenoise

type IItype IItype II

BF tonenoise

type III

400

00.5 1 2 5 10 20

-95

-90

-80

-70

-60

-50

-40

-30

-20

Frequency, kHz

Rat

e, S

pike

s/s

Rat

e, S

pike

s/s

dB atten

Sound Level0

Rat

e

1.25 2

300

05 10 20

2030405060708090

100

Frequency, kHz

100

200

0Sound Level

Rat

e

300

200

100

BF

Figures by MIT OCW.

Antidromic stimulation•record from neuron•shock its axon

DAS

VCN

DCN

fusiform

giant

vertical

recordingelectrode

stimulatingelectrode

recordingelectrode

stimulatingelectrode

recordingelectrode

stimulating electrode

recordingelectrode

stimulating electrode

Figures by MIT OCW.

DCN: “Principal” cells are type III and type IV units

•“Island of excitation” & “Sea of inhibition”•BF rate-level curve inhibited at high levels•Noise rate-level curve ~ monotonic

Rat

e, sp

ikes

/sR

ate,

spik

es/s

1.25 2

300

05 10 20

2030405060708090100

Frequency, kHz

Frequency, kHz

50

100

150

100

200

0

0Sound Level

Sound Level

Rat

eR

ate

400

05 10 20 50

25

35

45

55

65

75

8595

dB attn

TYPE IIITYPE III

TYPE IVTYPE IV

Evidence:Antidromic stimulation (Young 1980)Intracellular recording and labeling (Rhode et al. 1983, Ding et al. 1996)

SpontSpont

Figures by MIT OCW.

Neural circuitry underlying DCN physiology:type II units inhibit type IV units

Rat

e, sp

ikes

/s

Frequency, kHz

50

100

150

0Sound level

Rat

eR

ate

400

05 10 20 50

25

35

45

55

65

75

8595

dB attn.TYPE IVTYPE IV

TYPE IITYPE II

SpontSpont

400

00.5 1 2 5 10 20

-95

-90

-80

-70

-60

-50

-40

-30

-20

Frequency, kHz

Rat

e, sp

ikes

/sdB attn.BF

Sound level0

300

200

100

BF tonenoise

"Reciprocal" responses

Giant

Fusiform

Vertical

Figures by MIT OCW.

Classic experiment: type II units inhibit type IV units• multiunit recording Voigt & Young (1980, 1990)

Spik

es/S

econ

d

Cross-correlogram

Milliseconds-10 -5 0 5 10

10

20

30

-20

-10

400

300

200

100

0110 60 10

BF Tone

Level, dB Attn

NoiseRat

e, S

pike

s

Rat

e, S

pike

s

200

100

0-25 25 75

BBN

BF

Level,dB

type IV firing rate given type II fires at t=0

inhibitory trough

Cross-correlogramtype IV firing rate given type II fires at t=0

inhibitory trough

-

type II unit type IV unittype II unittype II unit type IV unit

Figures by MIT OCW.

DCN physiology so far…

IV ~ principal cells

II

auditory nerve

~ vertical cells

+

+

• 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

• (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?

0.5 1 5 10 40

Frequency (kHz) Frequency (kHz)

10

20

30

40

50

60

70

80

Rat

e (s

pike

s/se

c)

dB attn

0.5 1 10 40

Data

Model

Spont.

Rat

e (s

pike

s/se

c)

200

0

100

20 d

B

200

Type IV unit response map

spec

trum

leve

l

Notch noise stimuli

spec

trum

leve

lsp

ectr

um le

vel

Notch noise stimuli

Upper Inhibitory SidebandUpper Inhibitory Sideband

Figure by MIT OCW.

DCN notch noise sensitivity due to wideband inhibition

Broadband noise

AN input to type IV unit

frequency

leve

lle

vel

AN input to WBI

Notch noise

frequency

• strong AN input dominates

• type IV response is excitatory

• type IV loses greater portion of its excitatory input

• WBI input dominates

• type IV response is inhibitory

Nelken & Young 1994

WBIExcitatory

Inhibitory

Frequency

IV

Figure by MIT OCW.

PVCN: is the D-stellate cell the wideband inhibitor?

• such responses arise from radiate or stellate neurons (Smith & Rhode 1989)

• stellate cells send axons dorsally into the DCN, thus called “D-stellate cells” (Oertel et al. 1990)

• D-stellate cells are inhibitory (Doucet & Ryugo 1997)

• broadly-tuned, onset-chopper units are found in the PVCN (Winter & Palmer 1995)

• typically respond better to broadband noise than to tones

5-5

-15-25-35-45-55-65-75-85-95

-1051000050001000

Frequency (Hz)

Rel

ativ

e to

ne le

vel (

dB) 500

400

300

200

100

0100 50 0

1000

00 10 20

Noise

BF tone

Level, dB attn

Rat

e, sp

ikes

/s

Figure by MIT OCW. DCN

PVCN

DCN

PVCNa

Figure by MIT OCW.

Summary: Circuitry of DCN deep layer

Excitatory inputAN fibers?

Type II inhibitory inputs (strong)

UIS from ? source (weak)

Soun

d le

vel

Frequency

Excitatory

Inhibitory

400

300

200

100

0110 60 10

BF Tone

Level, dB attn

NoiseRat

e, sp

ike/

s

IV

Best frequency

500

400

300

200

100

0100 50 0

1000

00 10 20

Noise

BF tone

Level, dB attnR

ate,

spik

es/s

Inhibitory

Excitatory

Spirou and Young 1991

type IItype II

W.B.I.W.B.I.

“reciprocal” response properties

Figures by MIT OCW.

Summary of DCN anatomy and physiology

NonauditorySomatosensory

AuditoryVestibular

granule

fusiform

• vertical cell• type II unit• narrowband inhibition

D• D-stellate cell• onset-chopper• wideband inhibition




• Physiology of the DCN– diverse response properties– complex interconnections– highly nonlinear

• Functional considerations





• Functional considerations

Filtering by the pinna provides cuesto sound source location

Human

A

-15.

-15.

15.

60.

90.

0.

2 3 5 7 10 15 20

10

0

5

-5

-10

-15

-20

Frequency (kHz)

Tran

sfor

mat

ion

(dB

)“Head Related Transfer Function ” (HRTF)

Out

er e

ar g

ain

-15°-15°0°0°

+15°+15°

“first notch” frequency changes with elevation“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

• null in DCN population response may code for sound source location

Reiss & Young2005

May 2000

Physiology ⇒

Behavior ⇒

Figures by MIT OCW.

30

-100

1020

30

-100

1020

-15dB

-35 dB

-55 dB

-75 dB

-95 dB300

3 5 10 30

3 5 10 300

100

200

Frequency / kHz

Stimulus notch frequency

Rat

e / s

pike

s per

seco

ndR

ate

/ spi

kes p

er se

cond

Gai

n / d

BEl = 30o, Az = 15o

El = 30o, Az = -15o

El = 30o, Az = -15o

El = 30o, Az = 15o

spont.



• Anatomy of the DCN– more complex than other CN subdivisions– receives nonauditory inputs– has similar organization to cerebellar cortex


• Functional considerations– coding sound source location based on pinna cues

DCN is a “cerebellum-like structure”

Generic cerebellum-like structure

descending auditorydescending auditory

somatosensorysomatosensory

cochleacochlea

“plastic” synapses“plastic” synapses

Predictive Inputs :Corollary discharge signalsHigher levels of the same modalityOther sensory modalities (e.g. proprioception)?

Granule layer

Molecular layer

Principal cell layer

Sensory input layer

Input from a sensory surface

Figure by MIT OCW.

Synaptic plasticity: Long-Term Potentiation (LTP)

• “Classical” LTP demonstration at the hippocampal CA3-CA1 synapse• LTP evoked by tetanic stimulation (mechanism involves NMDA receptors)

Tzou

nopo

ulos

2004

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

• BUT the fish generates its own electric fields:• tail movements• ventilation

⇒ cerebellum-like ELL helps solve this problem Bell 2001

Figures by MIT OCW.

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





• 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

• percept of noise, ringing, buzzing, etc.

• affects up to 80% of the population

• 1 in 200 are debilitated

• (not voices in the head)

This makes no sense!

So why DCN? Because tinnitus…

• involves plasticity

• may involve somatosensory effects

Levine 1999





• 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 UniversityPress.

Slide 7: Ehret G, Romand R, eds (1997) The Central Auditory System. New York: Oxford UniversityPress.

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: Springer-Verlag.

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.


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.


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.


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 Neurobiol13:744-750.

HST.722 Brain Mechanisms of Speech and Hearing … Brain Mechanisms for Hearing and Speech Course Instructor: ... • Physiology of the DCN – diverse response properties – complex

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