1. Hair Cells Vestibular Classics February 2, 2007 Isabel Acevedo

2. Why hair cells? Sensory receptors of the vestibular and auditory systems in all vertebrates. Transduces mechanical stimuli into biological signals that are presented to the brain by afferents.

3. Hair Cell Morphology Cuticular Plate

4. Hair Cell Morphology Adapted from Pickles & Corey 1992 TL Types of Links: Kinocilial Links (KL) Ankle Links (AL) Shaft Links (SL) Upper Lateral Links (UL) Tip Links (TL) AL & SL

5. Stereocilia Growth 1 st Step: Stereocilia appear to elongate 2 nd Step: Stereocilia increase in width 3 st Step: Stereocilia increase in length Tilney et al, 1986.

6. Hair Cell Types Dickman in Fundamental Neuroscience, 2nd ed. (2002)

7. Hair Cell Communication Afferent Innervation: heterogenous population of fibers, whose somata are located in Scarpa’s ganglion, that convey hair cell response to the brainstem & cerebrum. Excitatory amino acids such as aspartate & glutamate are the neurotransmitters at the synapse between the receptor cell & afferent fibers Efferent Innervation: fibers originating in the medulla, at the level of the vestibular nuclei, that control the activity of hair cells. These fibers contain acetylcholine and calcitonine gene as neurotransmitters and are activated by behaviorally arousing stimuli or by trigeminal stimulation.

8. Accessory Structures Semicircular Canals Angular Acceleration Otolith Organs Linear Accelerations Dickman in Fundamental Neuroscience, 2nd ed. (2002)

9. Transduction Conversion of mechanical energy into electrical charges. –External mechanical stimulus causes hair cells to move –Appropriate mechanical stimulus modulates an ionic current flow from endolymph into apical end.

10. Transduction: In Vitro Hudspeth & Corey 1977Dickman in Fundamental Neuroscience, 2nd ed. (2002)

11. Transduction: In Vitro Hudspeth and Corey, 1977

12. Transduction: In Vivo IONPerilymphEndolymph Sodium (mM) 1411.3 Potassium (mM) 6157 Chloride (mM) 121132 Bicarbonate (mM) 1831 Calcium (mM) 0.60.0023 Ionic Composition of Fluids Dickman in Fundamental Neuroscience, 2nd ed. (2002)

13. Transduction: Negative Feedback Mechanical stimulus towards kinocilium ↑[K + ] i Depolarization ↑[Ca 2+ ] i Activate voltage-gated Ca 2+ channels ↓[K + ] i Ca 2+ activated K + (BK) channels Release neurotransmitters (Asp & Glu) Low Intensity High Intensity Fettiplace & Fuch, 1999.

14. Transduction: Calcium Channels Two types of Ca 2+ buffers. –Immobile buffers (pumps & exchangers): slow release of Ca 2+ into the presynaptic cytoplasm. –Mobile buffer (Ca 2+ binding proteins like calbindin-D 28k ): cause presynaptic [Ca 2+ ] i to fall very quickly by sequestering nearly all free Ca 2+ within 100 μs after Ca 2+ channels close.

15. Gating Springs Pickles & Corey, 1992.

16. Gating Springs Lenzi & Roberts, 1994.Pickles & Corey, 1992.

17. Adaptation Hair bundle is unlikely to develop so accurately that the sensitive transduction apparatus is perfectly poised at is position of greatest mechanosensitivity. Necessary mechanism to compensate for developmental irregularities and environmental changes: adjust the tension at the gating springs. If tip links are the gating springs, the most likely possibility is that the anchoring points are repositioned. Depends on [Ca 2+ ] i. Pickles & Corey, 1992.

18. Site of Transduction Hudspeth: Extracellular potential change was greatest around the top of the bundle. Ca 2+ -sensitive fluorescent dye: Large fluorescence signals observed in the apical cytoplasm, immediately beneath the hair bundle.

19. Morphologic Polarization Dickman in Fundamental Neuroscience, 2nd ed. (2002) Zakir, et al., 2002 Si, et al., 2002

20. Regeneration

21. Summary Hair Cells are the receptors of mechanical stimuli. Hair cells transduce mechanical stimuli to be presented to and analyzed by the brain. Hair Cells are heterogeneous agencies of transduction by virtue of their: morphological and physiological differences; varying complements of the transmitters and modulators and their receptors and; by the possibility that they behave differently in regard to resting and stimulated modes and adapt differently.