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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

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DCN

VCN AN

The cochlear nucleus

AN fibers terminate in a “tonotopic” or “cochleotopic” pattern

AVCN

PVCN

DCN36.0 kHz

10.2 kHz

2.7 kHz

0.17 kHz

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Major subdivisions of the cochlear nucleus

Spherical bushy

Globular bushy Multipolar

Octopus

Summary of pathways originating in the cochlear nucleus

SBC

GBC MAOA

Inferior colliculus

Lateral lemniscus

Superior olive

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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 ???

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

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DCN

PVCN

I.C.

SomatosensoryAuditory

Vestibular

TD

?

?

granule

giant

fusiform

auditory nerve

stellategolgi

cartwheel

vertical

Kanold Young2001

Tzounopoulos 2004

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

Eric Young

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Response Map classification scheme

Young 1984

~ Auditory Nerve increasing inhibition

DCN: Vertical cells are type II and type III units

type II BF

BF tonenoise

type III

•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)

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Antidromic stimulation

DAS

VCN

DCN

fusiform

giant

vertical

recordingelectrode

stimulatingelectrode

recordingelectrode

stimulating electrode

•record from neuron•shock its axon

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

spont

type III

•“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)

type IV

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

type II BF

BF tonenoise

type IV

spont

giant

fusiform

vertical

Young & Brownell 1976

“reciprocal” responses

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

inhibitory trough

Cross-correlogram

Classic experiment: type II units inhibit type IV units

type II unit type IV unit

• multiunit recording Voigt & Young (1980, 1990)

Voigt & Young 1980,1990

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DCN physiology so far…

IV

• type II units inhibit type IV units

• BUT this analysis based on pure-tone responses

⇒ what happens with more general stimuli???

II

auditory nerve

~ vertical cells

~ principal cells

+

+

Inhibition from type II units doesn’t account for everything

Type IV unit response map

spec

trum

leve

l Notch noise stimuli

• (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?

Upper Inhibitory Sideband

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Notch noise

frequency

DCN notch noise sensitivity due to wideband inhibition

• strong AN input dominates

• type IV response is excitatory

Broadband noise

AN input to type IV unit

frequency

leve

lle

vel

AN input to WBI

• type IV loses greater portion of its excitatory input

• WBI input dominates

• type IV response is inhibitory

WBI

Nelken & Young 1994

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)

DCN

PVCN

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

• typically respond better to broadband noise than to tones

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Summary: Circuitry of DCN deep layer

Spirou and Young 1991

type II

type IIW.B.I.

W.B.I.

“reciprocal” response properties

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

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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 cuesto sound source location

“Head Related Transfer Function” (HRTF)

Out

er e

ar g

ain

Geisler 1998

-15°0°

+15°

“first notch” frequency changes with elevation

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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

Young et al. 1992

Reiss & Young2005

May 2000

Physiology ⇒

Behavior ⇒

vary notch freq

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

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DCN is a “cerebellum-like structure”

Bell 2001

Generic cerebellum-like structure

descending auditory

somatosensory

cochlea

“plastic” synapses

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

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Electric fish provide clues to cerebellum-like function

black ghost knifefish (Apteronotus albifrons)

http://nelson.beckman.uiuc.edu/

electric organ

electric organ discharge

(EOD)

• electric fields detected by electric lateral line• afferent activity transmitted to electric lateral line

lobe (ELL), analogous to DCN

Electric fields provide information about nearby objects

Water flea(prey)

Larger animal (predators, other knifefish)

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

⇒ cerebellum-like ELL helps solve this problem

Zakon 2003

Bell 2001

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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

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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

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

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References 1. Bell CC (2001) Memory-based expectations in electrosensory systems. Curr Opin Neurobiol 11:481-487.

2. Ding J, Benson TE, Voigt HF (1999) Acoustic and current-pulse responses of identified neurons in the dorsal cochlear nucleus of unanesthetized, decerebrate gerbils. J Neurophysiol 82:3434-3457.

3. Doucet JR, Ryugo DK (1997) Projections from the ventral cochlear nucleus to the dorsal cochlear nucleus in rats. J Comp Neurol 385:245-264.

4. Kanold PO, Young ED (2001) Proprioceptive information from the pinna provides somatosensory input to cat dorsal cochlear nucleus. J Neurosci 21:7848-7858.

5. Levine RA (1999) Somatic (craniocervical) tinnitus and the dorsal cochlear nucleus hypothesis. Am J Otolaryngol 20:351-362.

6. May BJ (2000) Role of the dorsal cochlear nucleus in the sound localization behavior of cats. Hear Res 148:74-87.

7. 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.

8. 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.

9. Reiss LA, Young ED (2005) Spectral edge sensitivity in neural circuits of the dorsal cochlear nucleus. J Neurosci 25:3680-3691.

10. Rhode WS, Oertel D, Smith PH (1983) Physiological response properties of cells labeled intracellularly with horseradish peroxidase in cat dorsal cochlear nucleus. J Comp Neurol 213:426-447.

11. Smith PH, Rhode WS (1989) Structural and functional properties distinguish two types of multipolar cells in the ventral cochlear nucleus. J Comp Neurol 282:595-616.

12. 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.

13. Tzounopoulos T, Kim Y, Oertel D, Trussell LO (2004) Cell-specific, spike timing-dependent plasticities in the dorsal cochlear nucleus. Nat Neurosci 7:719-725.

14. Voigt HF, Young ED (1980) Evidence of inhibitory interactions between neurons in the dorsal cochlear nucleus. J Neurophysiol 44:76-96.

15. Voigt HF, Young ED (1990) Neural cross-correlation analysis of inhibitory interactions in dorsal cochlear nucleus. J Neurophysiol 64:1590-1610.

16. Weedman DL, Ryugo DK (1996) Projections from auditory cortex to the cochlear nucleus in rats: synapses on granule cell dendrites. J Comp Neurol 371:311-324.

17. 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.

18. Wright DD, Ryugo DK (1996) Mossy fiber projections from the cuneate nucleus to the cochlear nucleus in the rat. J Comp Neurol 365:159-172.

19. Young ED (1980) Identification of response properties of ascending axons from dorsal cochlear nucleus. Brain Research 200:23-38.

20. Young ED (1984) Response characteristics of neurons of the cochlear nuclei. In: Hearing Science (Berlin CI, ed), pp 423-460. San Diego: College-Hill.

21. 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.

22. 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.

23. Zakon HH (2003) Insight into the mechanisms of neuronal processing from electric fish. Curr Opin Neurobiol 13:744-750.

24. Zhang S, Oertel D (1994) Neuronal circuits associated with the output of the dorsal cochlear nucleus through fusiform cells. J Neurophysiol 71:914-930.