Radha Kalluri - US grants

[unreadable] DESCRIPTION (provided by applicant): Sensory organs are often populated by different cell types, each of which has specializations that allow it to process and transmit different modes of information. Differences in the firing patterns of vestibular afferent neurons suggest that a division of labor exists in the vestibular periphery. Based on their in vivo spike timing regularity, afferent neurons of the mammalian vestibular periphery are commonly described as ranging from highly regular to highly irregular. This diversity of firing patterns is thought to reflect the vestibular periphery's ability to code different aspects of sensory information. For example, irregular neurons are believed to be important for coding fast temporal changes in the stimulus, whereas regular neurons are believed to be important for coding slower changes. Despite extensive characterizations of neuronal responses to head movements in vivo, little is known about the origin of these firing patterns. The goals of this proposal are to use electrophysiological measurements coupled with biophysical models to identify neuronal specializations that are needed to support differences in firing patterns. Recent in vitro studies show that the somata of vestibular afferent neurons express diverse groups of ionic conductances, consistent with an earlier model which proposed that a vestibular afferent neuron's intrinsic membrane properties plays a role its ability fire different patterns of action potentials. To link in vitro and in vivo characterizations, I propose to characterize neuronal firing patterns by applying pseudo-synaptic stimuli to vestibular neurons in vitro. To study their influence on firing patterns, I will isolate conductances pharmacologically and with dynamic clamp techniques. I will characterize the kinetics of the relevant conductances and develop biophysical models to represent the intrinsic properties of different classes of vestibular afferent neurons. The models will explore the combined influence of intrinsic membrane properties and number and size of converging inputs in shaping firing patterns. By combining novel stimuli, dynamic clamp techniques, and biophysical models, our experiments will provide a way to link high-quality biophysical characterizations of specific ion conductances to functional in vivo data. The proposed research is focused on understanding how the electrical properties of vestibular neurons affect their ability to carry sensory information. In vitro studies characterizing the ion channels underlying neural activity are crucial for understanding how genetic mutations in these channels can cause hearing and balance disorders. [unreadable] [unreadable] [unreadable] [unreadable]