Identification of cell types in the central nucleus of the mouse inferior colliculus

Oregon Health & Science University, Portland OR

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): The inferior colliculus (IC) is the major subcortical integrator of the auditory system. Its central nucleus (the ICC) receives ascending input from almost all lower auditory brainstem regions. These inputs are organized within the ICC's microcircuit by diverse cell types that are largely undefine, neurotransmitter content, and intrinsic properties, these parameters do not correlate in such a way to define functional subtypes of neurons. This presents a major barrier to our understanding of sound encoding in the brain as well as auditory pathologies such as chronic tinnitus, which is associated with hyperactivity in the IC driven by a subset of cells that undergo marked changes in biophysical properties. Therefore, I will utilize genetic markers as a novel approach to assessing neuronal subtypes and their functional roles in the ICC. I have identified three transgenic mouse lines that I believe to label subtypes of inhibitory and excitatory cells in the IC and made paired recordings to begin functional characterization of the local circuit for the first time. I hypothesize that geetic markers will define discrete sets of neuronal subtypes that mediate the intrinsic computational capacity of the IC. Specifically, I predict that somatostatin+ cells, based on evidence for local excitation, are excitatory interneurons that mediate intralaminar excitation to widen the dynamic range of the microcircuit. Parvalbumin+ cells, based on commissural fiber labeling, likely mediate inhibitory intercollicular interactions. Finally, collagen beta(1-O)galactosyltransferase 2 cells, distinctly large and excitatory, likely integrate information from the microcircuit to projet to the auditory thalamus. The purpose of this proposal is to test: (1) whether cellular subtypes can be defined based on genetic markers and (2) how cell types interconnect to inform a local circuit diagram for the ICC. In Aim 1 I will take advantage of Cre transgenic mouse lines to target specific neuronal populations, enabling me to selectively visualize and manipulate genetically defined cell populations. I will determine whether the reporter lines mentioned above identify functionally discrete cell types via assay of intrinsic biophysical properties with in vitro electrophysiology, morphology, and neurotransmitter content. This approach will allow me to define cellular subtypes in the IC in a way that has not yet been possible. In Aim 2 I will test th functional connectivity of local circuitry with optogenetic stimulation of molecularly defined cell types, paired recordings within laminae, and intracranial injections of Cre-dependent virus that drives fluorophore expression to visualize efferent fiber tracts. The proposed research answers fundamental questions about the internal structure of the IC and utilizes novel resources to unravel a brain circuit with cellular resolution. This research will provide cellular mechanisms underlying the essential role of local circuitry in neural processing of sound in the IC. This in trn will provide insight into how dysfunctions within this circuit lead to common disorders of the auditory system.