1. Lecture 7

2.  Note in particular ◦ Insertion of stereocilia into cuticular plate ◦ Basal body (rudimentary kinocilium) ◦ OHCs contain extensive subsurface cisternae and intracellular structures concentrated around the edges of the cell (In contrast with IHCs) ◦ Afferent and efferent nerve endings around base of cells 2

3. Kinocilia are found on the apical surface of hair cells and are involved in both the morphogenesis of the hair bundle and mechanotransduction. Vibrations (either by movement or sound waves) cause displacement of the hair bundle, resulting in depolarization or hyperpolarization of the hair cell. The depolarization of the hair cells in both instances causes signal transduction via neurotransmitter release.

4. 4 OHC

5. 5 (This could be an error – efferents are thought to terminate on afferent endings rather than directly on IHC) IHC

6.  Perilymph ◦ Similar in composition to other extra-cellular fluids & CSF ◦ Cochlear aqueduct connects ST (near base) to subarachnoid space  Are some differences in composition ◦ Very high in Na +, very low in K + ions ◦ Source – probably blood vessels within cochlea 6

7.  Endolymph ◦ Similar in composition to intra-cellular fluids (unusual) ◦ High in K +, low in Na + ions ◦ Source unclear – perhaps derived from perilymph  Stria vascularis plays important role in maintaining ionic composition 7

8.  Note that reticular lamina (not BM) forms the boundary between endolymph & perilymph in ST ◦ Hence the distinction between scala media (bounded by BM) and endolymphatic space ◦ While hair bundles are exposed to endolymph, lateral walls & bases are bathed in perilymph 8

9.  Stapes vibrations set up initial pressure waves in SV ◦ Correspond to normal propagation of sound in fluid  Very fast, longitudinal waves ◦ Wavelength much greater than dimensions of scala vestibuli => instantaneous fluid pressure is more or less the same throughout SV ◦ Vibrations in SV do not pass through helicotrema (except for very low frequencies) 9

10.  Reissner’s membrane no impedance barrier – ‘acoustically transparent’  Result is a pressure differential across BM/organ of Corti complex, causing it to vibrate between points of attachment 10

11.  Note – Reissner’s membrane probably does not vibrate with same pattern as (parallel to) BM as suggested in the figure  Fluid pressure eventually released at (flexible) round window 11

12.  Although the initial fluid pressure at any instant is the same throughout SV, ... the BM does not simply vibrate as one unit in response to pressure differential across it  Rather, interaction between fluid pressures and BM mechanics results in a wave of displacement of BM ◦ Wave appears to travel (relatively slowly) from base to apex of cochlea 12

13. Solid lines represent travelling wave in response to a (low frequency) pure tone at four successive instants in time (as numbered). Dashed lines represent static ‘envelope’ of wave (As first observed by George von Békésy) 13 Distance along cochlea (Base)(Apex) Displacement

14. ◦ Entire BM/organ of Corti complex (also TeM) vibrates ◦ Can be regarded as a transverse wave, similar to waves (ripples) on surface of water ◦ Direction of travel results from decrease in BM stiffness (that accompanies increase in its width) from base to apex  Wave appears to travel from base to apex regardless of whether the stimulus is applied at the base of cochlea or elsewhere 14

15.  Wave slows and builds in amplitude as it travels, then peaks and decays almost immediately  For a particular signal frequency, waves are contained within ‘static’ envelope (dotted lines in figure)  Position of peak along BM depends uniformly on signal frequency – place-frequency map  See also animations at www reference! 15

16.  For high frequency signals, maximum BM response (peak of travelling wave envelope) is near the base of the cochlea  Lower frequencies peak towards apex  Also due primarily to BM stiffness decrease from base to apex 16

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18.  Response (vibration) at a particular site is also extremely sharply ‘tuned’ to this best (‘characteristic’) frequency ◦ (If you change frequency slightly, the response drops dramatically)  Sharply tuned place-frequency map is a primary basis of frequency selectivity in the auditory system ◦ (Perhaps not at low frequencies)  Response for a particular frequency spreads much more into adjacent ‘higher-frequency’ (basal) regions than ‘lower-frequency’ (apical) regions 18

19.  ‘Vertical’ displacements of BM/organ of Corti, TeM give relative shear between reticular lamina & TeM ◦ Points at which BM, TeM ‘hinged’ are important  … which causes HC stereocilia (hair bundles) to be deflected 19

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21.  Classical view – ◦ Hair bundles defelected away from modiolus for BM upward associated with excitation ◦ Towards modiolus for BM downward compresses the tip links and is associated with inhibition ◦ Relationship between BM displacement & HC bundle deflection is evidently highly complex 21

22.  Achieved by IHCs ◦ Are ‘true receptor cells’ ◦ (Vast majority of NVIII afferents synapse with them)  Endolymph is at a steady potential (voltage) of ~ +80 mV (relative to perilymph) ◦ The endocochlear potential (EP) ◦ Maintained by metabolic ion-pumping mechanism of stria vascularis 22

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24.  HCs (like most cells) also maintain a steady internal potential ◦ The intracellular (resting) potential ◦ Maintained by cellular ion transfer processes ◦ ~ –45 mV in IHCs ◦ ~ –70 mV in OHCs 24

25.  Combination of potentials acts as a ‘battery’ ◦ Recall that stereocilia contains ion channels  Certain percentage are always open ◦ ‘Battery’ drives a steady (‘DC’) ionic current (mainly K + ) from endolymph, through ion channels, into HC (and out through basolateral wall)  However, it’s clear that deflection of stereocilia is the mechanical input to the HCs ◦ OHC bundles – directly coupled to TeM ◦ IHC bundles – probably via intervening fluid only ◦ Recall rigidity of stereocilia – ‘pivot’ at point of attachment to HC, rather than ‘bend’ (as often described) 25

26.  In quiet, the system is in equilibrium – essentially steady (DC) potentials, currents  Deflections of hair bundles thought to open or close ion channels ◦ Cross-links at tips of stereocilia physically them pull open?! ◦ Cause variations in ion currents flowing through cell  Mechano-electrical transduction 26

27.  Deflection of hair bundle away from modiolus ◦ Opens ion channels ◦ Increases current into HC ◦ Depolarises cell  (Resting potential heads back towards zero) 27 HC resting potential (negatively polarised) Influx of K + ions depolarises cell 0 V + –

28.  Depolarisation of IHCs causes release of neurotransmitter at base of cell ◦ Neurotransmitter probably glutamate ◦ Ca 2+ ions probably mediate release ◦ Initiates (increases likelihood of) firing of primary afferent neurons  And conversely, deflection of bundle towards modiolus … reduces likelihood of firing of primary afferents 28

29.  Can be steady (DC) or fluctuating (AC) over time  ‘Resting’ potentials (DC) ◦ Endocochlear potential (+80 mV) ◦ HC intracellular resting potentials  HC receptor potentials ◦ See figure – responses to 50-ms tone bursts (at various frequencies as marked) ◦ Receptor potential is the intracellular voltage change in response to sound 29

30. 30 Hair cell receptor potentials

31.  Have both a fluctuating (AC) and a steady (DC) component ◦ AC component broadly follows waveform of stimulus (see upper traces of figure) ◦ But the average amplitude of the AC waveform is not the same as when the stimulus is off (at the end of the burst) ◦ The slight positive shift in the average AC response is equivalent to a DC (steady) component superimposed on it 31

32. ◦ Note that DC component is depolarising (positive- going) (Recall that in IHCs, depolarisation causes neurotransmitter release) ◦ Also note that the AC component of the receptor potential gets smaller with increasing stimulus frequency & the DC relatively larger 32

33.  Massed effects of electrical activity of individual cells. Can be recorded at various sites in & around cochlea. (Potentially clinically useful) ◦ Cochlear microphonic – voltage recorded as extracellular correlate of AC component of receptor currents/potentials. Predominantly due to activity of OHCs ◦ Summating potential – extracellular correlate of DC component of receptor currents. Due to both IHCs & OHCs(?) 33

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35. ◦ Compound action potential – summed activity of a number primary afferent neurons firing together at the onset of a stimulus  Typically recorded in response to clicks or tone-bursts  Distinct negative-going peak within ~ 1 ms of transient stimulus, denoted N 1 (secondary N 2 peak sometimes seen) 35