Sensory organs are often populated by different cell types, each of which has specializations that allow it toprocess and transmit different modes of information. Differences in the firing patterns of vestibular afferentneurons suggest that a division of labor exists in the vestibular periphery. Based on their in vivo spike timingregularity, afferent neurons of the mammalian vestibular periphery are commonly described as ranging fromhighly regular to highly irregular. This diversity of firing patterns is thought to reflect the vestibular periphery'sability to code different aspects of sensory information. For example, irregular neurons are believed to beimportant for coding fast temporal changes in the stimulus, whereas regular neurons are believed to beimportant for coding slower changes. Despite extensive characterizations of neuronal responses to headmovements in vivo, little is known about the origin of these firing patterns. The goals of this proposal are touse electrophysiological measurements coupled with biophysical models to identify neuronal specializationsthat are needed to support differences in firing patterns. Recent in vitro studies show that the somataofvestibular afferent neurons express diverse groups of ionic conductances, consistant with an earlier modelwhich proposed that a vestibular afferent neuron's intrinsic membrane properties plays a role its ability firedifferent patterns of action potentials. To link in vitro and in vivo characterizations, I propose to characterizeneuronal firing patterns by applying pseudo-synaptic stimuli to vestibular neurons in vitro. To study theirinfluence onfiring patterns, I will isolate conductances pharmacologically andwith dynamic clamptechniques. I will characterize the kinetics of the relevant conductances and develop biophysical models torepresent the intrinsic properties of different classes of vestibular afferent neurons. The models will explorethe combined influence of intrinsic membrane properties and number and size of converging inputs inshaping firing patterns. By combining novel stimuli, dynamic clamp techniques, and biophysical models, ourexperiments will provide a way to link high-quality biophysical characterizations of specific ion conductancesto functional in vivo data.The proposed research is focused on understanding how the electrical properties of vestibular neuronsaffect their ability to carry sensory information. In vitro studies characterizing the ion channels underlyingneural activity are crucial for understanding how genetic mutations in these channels can cause hearing andbalance disorders.
