VESTIBCELLDYNAMICS · Voltage and calcium dynamics and synaptic transmission within neuronal microcircuits in the vestibular cerebellum

A fundamental goal of neuroscience is to understand how neurons communicate and encode information. Information transfer between neurons is classically thought to be mediated through rapid all-or-none membrane potential changes, called action potentials (APs), which lead to presynaptic calcium entry and neurotransmitter release. Recently, however, analog transmission has been detected through passive propagation of subthreshold depolarization down axons. Dendrites too exhibit active and passive properties. Technical constraints have made electrophysiological recordings from fine neuronal processes difficult, but advancements in optical imaging have opened avenues for monitoring fluctuations in membrane voltage and calcium signals with increased temporal and spatial resolution. The laboratory where I will do my postdoctoral work is developing novel methods for optical detection of membrane voltage. We will use these optical techniques to study both subcellular membrane potentials and rapid intracellular calcium changes in fine axonal and dendritic processes. The vestibulocerebellum is the oldest part of the cerebellum and processes specific proprioceptive information. This region is anatomically well-defined, with clearly identifiable cell types. While circuit function and cell connectivity in this region are well understood, little is known about how information is processed within the granule cell (GC) layer. Notably, these cells are electrically compact and may exhibit analog signaling. This work will provide novel insight into depolarization and calcium signaling in GC axons and fine dendrites of inhibitory stellate cells that they target. I will address the following questions: 1. Do subthreshold depolarizations propagate and elicit calcium influx in GC axon terminals? 2. Do subthreshold depolarizations influence neurotransmitter release in GC axon terminals? 3. How do APs and subthreshold depolarization propagate and sum along thin dendrites of stellate cells?