C 1/3: Brain Circuit Validation Core

Thomas Kash

Chronic ethanol exposure and stress alter synaptic transmission and neuronal excitability in a number of brain circuits that control acquisition, maintenance, relapse and escalation of ethanol seeking and drinking. Work from previous INIA cycles/projects has generated hypotheses about how specific physiological changes in defined neuronal populations and circuits affect these ethanol-related behaviors. In the INIA-Stress renewal, multiple projects will test these hypotheses by manipulating and measuring neuronal and circuit function using multiple viral based genetic approaches in several distinct mouse Cre- recombinase driver lines. The central goal of this core is to provide initial validation of all mouse lines, and ongoing validation of all viral tools used in the consortium. While multiple viral tools will be validated, the Designer Receptor Activated by Designer Drug (DREADD) based chemogenetic approach has emerged as a common tool across multiple projects and will represent the bulk of the effort. The DREADD technique, based on neuromodulation by G protein-coupled receptors, has many attractive features for neuron/circuit control and has been shown to be highly effective for probing circuit function in animal models. The services of this core will be provided to fill significant gaps in the literature and provide assistance to many of the INIA-Stress projects.