Behavioral Function of Forebrain Projections to Brainstem Gustatory Nuclei Revealed By Optogenetic Control of Cell-Type/Target-Specific Pathways

University Of Louisville, Louisville KY

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Abstract

The gustatory region of the nucleus of the solitary tract (NST) and parabrachial nucleus (PBN) play distinct roles in the control of taste-guided behaviors and are densely innervated by numerous ventral forebrain structures including the central nucleus of the amygdala (CeA). The extent to which such neuromodulatory circuits shape the distinct functional roles of the NST and PBN is unknown. This project is aimed at developing an experimental model system, new to the field of gustatory research, for addressing long-standing questions regarding the function of specific neural pathways in various aspects of taste-guided behavior. Specifically, we will use existing virus technologies to design an experimental platform that will enable isolation and manipulation of cell-type/target-specific circuits of the gustatory system. Study of the interactions between forebrain and brainstem gustatory circuits that participate in dietary selection is particularly relevant to our understanding of factors that contribute to overconsumption and obesity. We will use mice that express Cre- recombinase in somatostatin (Sst) neurons combined with viruses that infect axonal terminals and are retrogradely-transported back to the parent cell body (Herpes Simplex Virus (HSV)). The viruses contain floxed stop sequences (DIO) and encode: 1) enhanced yellow fluorescent protein (EYFP) and an excitatory light-activated ion channel (ChR2) or 2) EYFP and an inhibitory light-activated ion channel (eNpHR3.0). This ensures specific expression of transgenes in Sst-expressing neurons. Specific aim 1 will inject HSV-DIO- ChR2-EYFP and HSV-DIO-eNpHR3.0-EYFP into the NST or PBN. In vivo extracellular recording of CeA neurons will be made before, during, and after delivery of light pulses at various temporal frequencies. These experiments will demonstrate the utility of retrograde gene transfer techniques for bidirectional control of cell-type/target-specific gustatory pathways. Specific aim 2 will inject the same viruses bilaterally into the NST or PBN combined with bilateral optic fiber cannula implantation above the CeA to determine the effects of activation and inactivation of Sst-CeA neurons on: 1) concentration-dependent intake of quinine and sucrose and 2) conditioned taste aversion acquisition. These experiments will test the validity of our central premise that specific pathways carry particular gustatory-related functions, as opposed to particular neuron types. Successful completion of the proposed experiments will represent a significant advance within the field by permitting selective manipulation of taste circuits and characterization of their behavioral function. This model system also will be broadly-useful to the fields of behavioral neuroscience and optogenetic-assisted circuit mapping.