PROJECT SUMMARY/ABSTRACT The vestibular system encodes sensory information through two afferent subpopulations that fire spontaneously at intervals that are either regular or irregular. These timing features are critical for afferent function since irregular afferents encode high-intensity head movements using a temporal code while regular afferents integrate low-intensity head movements using a rate code. Afferent spike-timing regularity is thought to reflect the ion channel composition of the vestibular ganglion neurons that form the afferents. However, one cannot establish definitive relationships between ion channel composition in vestibular ganglion neurons and afferent spike-timing regularity without considering the impact of the vestibular efferents. Current in vitro assessments of the ion channel properties of vestibular ganglion neuron extract these neurons from the modulatory inputs that are present in the intact system. These inputs include the vestibular efferents, which tonically release acetylcholine and increase afferent excitability by closing inhibitory channels. My preliminary data shows this ion channel configuration favors regular spike-timing. By re-establishing efferent- input in vitro, we expect to better approximate firing patterns that occur in the intact system. We will then validate the alignment between in vitro firing pattern and established markers of afferent firing pattern based on the differential expression of molecular markers. Together, these data will characterize the role of the vestibular efferents in shaping afferent firing pattern. We plan to pursue the following aims: 1) Characterize the contribution of vestibular efferents to spike-timing regularity and 2) Determine whether adding efferent input better approximates their firing patterns in the intact system. Together, these data will assess the impact of vestibular efferents on spike- timing regularity in multiple afferent subpopulations found in specific regions of the vestibular epithelia. This proposal leverages the unique advantages of in vitro electrophysiology to reveal the biophysical properties that underlie afferent firing pattern and accordingly their encoding strategy. By establishing the role of the efferents in this process, this proposal will improve our ability to identify the features that distinguish regular and irregular afferents. Completion of these aims will significantly expand our ability to correlate ion channel measurements in vitro to afferent firing pattern in vivo, thereby significantly increasing the significance of our findings.