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Neurobiology of Salamanca, 20th May 2015

The : mechanics and transduction , and Pharmacology University College London

[email protected]

Not all tuning mechanisms use the same cellular design

BM Hair

cell frogs

reptiles

BM Hair birds

cell

Sound Soundinput

Sound Soundinput

BM Hair

cell mammals

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In non-mammals, hair cells are electrically tuned: Neural tuning = intrinsic tuning

Found in frog hair cells (Hudspeth et al); Turtle hair cells (Fettiplace et al.)

In mammals, neural tuning = tuning

Post-mortem

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The mammalian cochlea is a mechanical spectrum analyser

B A

Stapes Basilar membrane

Fluid Fluid in motion at Round rest window

BM stiffness high low

Does the spiral contribute to cochlear performance? Only in a minor way.

high frequencies

low frequencies

Sound enters from middle ear From Manoussaki et al., Phys Rev Letts E 2006

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Stapes Basilar membrane

Fluid Fluid in motion at Round rest window

d 2 x dx Simple m i  h i  k x  f (t) , oscillator i dt 2 i dt i i i

N 2 j i d xi dxi  dxi dxi1 dxi1  Gi  mi j  2  hi Ui (yi )  si 2     ki x  Gi aS (t) j1 dt dt  dt dt dt 

x = BM displacement ‘undamping’ y = tectorial membrane displacement

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What in silico models of the cochlea do: Inform intuition! Natural framework for functional genomics

They indicate that there may be : Cochlear gradients of the mechanotransduction channel Cochlear gradients of K channel densities A small degree of longitudinal coupling along the cochlea

From Robles & Ruggero, 2001

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Raw data from interferometry

BM velocity

normalised velocity (gain)

i.e. At low sound levels, there is amplification. The system is non-linear.

The original data: Sellick et al (1983)

40 dB gain

Methods: used Mossbauer effect , radioactive Co 57 chip on BM better: laser interferometry with reflectance from BM

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The mechanics of the basilar membrane

From mechanics to neural signal

tectorial membrane

basilar membrane

nanometres!

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Hair Cells

Inner hair cells (IHCs): one row, ~3500 total

Outer hair cells (OHCs): 3-5 rows, ~12000 total

A – depends on outer hair cells

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Sound

transduction in

IHC OHC

glutamate ACh

Auditory nerve fibres build audiograms

Tone level for extra action potential dB SPLpotential action dB for extra level Tone

FrequencykHz in kHz

From guinea pig, Evans 1972

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Each auditory nerve fibre responds best to a single frequency

Auditory nerve fibres are sharply tuned and have varying response thresholds.

Nerve fibers also show phase-locking (temporal coding) up to about 3000 Hz.

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