The dorsal cochlear nucleus integrates ascending auditory information with descending input from a variety of sources in the brain. Part of the descending information passes through a cell type, the unipolar brush cell (UBC), whose physiological role in the circuit is poorly understood. The current model suggests that UBCs act as relays to amplify descending information. However, their role is likely to be more complex than acting merely as relays. One reason is that UBCs receive highly specialized synapses with very unusual kinetics. Furthermore there are at least two major subclasses of UBC, one that expresses metabotropic glutamate receptor isoform mGluR1, and one that does not. This differential expression strongly suggests that the two classes have different roles in the processing of information. This proposal will test the hypothesis whether these two classes of UBC process synaptic activity differently.
The first aim will design a strategy for distinguishing between these two classes in physiological experiments, based on the differential expression of mGluR1. In the second aim, the synapses formed onto these different subclasses will be studied using whole- cell patch clamp, focusing particularly on activity-dependent changes in their synaptic strength. In addition, the functional effects of synaptic activation will be studied using current clamp.
The third aim will investigate how the expression of mGluR1 by one subclass of UBC affects the way it responds to synaptic activity. These studies are important, because they will examine the role of a poorly-understood cell that sits at a critical point in the auditory pathway. The experiments proposed here will be the first to examine how descending activity is transformed by UBCs, and may shed light on why multiple classes of UBC exist.
The dorsal cochlear nucleus plays a role in normal sound processing by integrating descending activity from many areas in the brain with incoming information about sounds. These experiments will directly address how descending activity is transformed by unipolar brush cells, which are a critical cell type within the DCN. In addition, th DCN has been implicated in tinnitus, so better understanding of the DCN network may yield therapeutic ideas for reducing the symptoms of tinnitus.
|Yang, Hua; Xu-Friedman, Matthew A (2013) Stochastic properties of neurotransmitter release expand the dynamic range of synapses. J Neurosci 33:14406-16|