Vestibular receptors encode information about head movements and send these signals through the vestibular nerve to the brain stem. In turn, receptors and afferents receive bilateral inputs from efferent fibers that originate in the brain stem. To date, the function of the efferent pathway has remained elusive. It has been suggested that efferents might provide information regarding imbalance in the activity on the two sides and play a role in vestibular compensation. In particular, efferents mainly affect activity of afferent with calyx terminals, which completely cover the basolateral walls of vestibular hair cells and provide a unique form of synapse present only in the vestibular periphery. Furthermore, there are two main types of efferent fibers, cholinergic and GABAergic. However, almost nothing is known regarding the innervation patterns, synaptic properties, receptor types, and differential effects of the two efferent pathways on vestibular afferent sensory coding. The goal of the present proposal is to investigate changes in afferent response properties mediated by efferent inputs from these two pathways and the underlying cellular mechanisms. The hypothesis, supported by preliminary results, is that efferent inputs change the firing properties and response patterns of afferents from phasic to tonic. The effect of muscarinic acetylcholine receptors (mAChR) on calyx membrane properties will be studied at the cellular level in vitro. Preliminary data suggest that activation of mAChRs results in a shift to tonic afferent responses mediated by changes in potassium channel activities present in calyces. The effect of GABAergic efferent inputs on membrane properties of calyx terminals will also be investigated in vitro. Preliminary results suggest that ~50% of calyces do not receive cholinergic efferents and might receive GABAergic inputs. Finally, the effect of the two efferent pathways will be studied on firing properties of afferent fibers in response to rotational movements in live animals (in vivo). Results of the experiments in this proposal can provide a leap in our understanding of feedback modulation of sensory coding in this example sensory system. This will be the basis for future studies in alert behaving animals in order to correlate neuronal and behavioral measures as well as studying the possible role of efferent inputs in vestibular compensation.
The role of the rich vestibular efferent innervation, which provides feedback inputs from the brain stem to the vestibular peripheral sensory epithelia is not known. The present proposal uses new a combination of immunohistochemistry, electrophysiology, and genetic approaches both in vitro and in vivo, to investigate changes in afferent response properties mediated by the cholinergic and GABAergic efferent pathways differentially. Results will provide a better understanding of the function of the efferent vestibuar system and the basis for new pharmacological approaches for improving compensation in patients with vestibular dysfunction.