Diverse synaptic mechanisms underlying the processing of peripheral vestibular information in mammals
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Sensation of head position through the vestibular system is critical for maintaining balance and various physiological functions. To provide head movement information with high fidelity, unique synaptic circuitry has evolved in the mammalian peripheral vestibular epithelium. Among sensory receptors, the hair cells (HCs), type I HCs are completely ensheathed by calyx-like afferent terminals, and type II HCs are contacted by conventional bouton-like afferent terminals. Type II HCs and afferents are also regulated by efferent inputs originating from the brain stem. It is intriguing to know how those specialized neuronal elements work in concert to mediate the peripheral vestibular function. Here, in the first part of this thesis, I investigated synaptic signals generated at synapses between HCs and calyx-containing afferents. I found that output signals from type I HCs were distinct from signals produced by type II HCs, as the former had more tonic waveform and were resistant to glutamate receptor blockade while the later resembled conventional signals resulting from quantal vesicular glutamate synaptic transmission. While both types of signals were excitatory, I showed that those unusual Type I HC signals alone could strongly drive firing rate increases in calyx-containing afferents and mediate vestibular-ocular reflexes (Dr. Kodama performed behavior tests). Therefore, this study demonstrates that peripheral vestibular function is mediated by highly distinct signals at type I and type II HC synapses. Because of their fast onset kinetics, signals generated at the type I HC to calyx synapses may facilitate the detection of quick head movements. In the second part of this thesis, I investigated how efferents modulate the peripheral vestibular function at individual types of synapses. Those efferent synapses showed strong short-term facilitation, indicating that they could provide powerful modulation during high-level activities. However, efferents were found to inhibit type II HC through α9 nicotinic acetylcholine receptors (nAChRs) and SK potassium channels while exciting calyx-containing afferents through neuronal type nAChRs. Such distinct effects possibly provide a mechanism for efferents to fine tune the gain and sensitivity of the vestibular periphery. By illustrating functional properties of diverse synaptic signals, this study has greatly contributed to our understanding of peripheral vestibular functions.