Localized structuring of neuronal output by inhibitory microcircuits is a fundamental component of neuronal information processing. Interneuron subpopulations contained within these microcircuits integrate afferent excitatory and inhibitory inputs, transforming these external signals into broad modulatory effects. Simple on-off dichotomies do not accurately account for the modeled variations in interneuron activity resulting from excitatory or inhibitory inputs alone. These modeled activity profiles position interneuron microcircuits as unique relays of incoming neurotransmission that may be able to generate distinct patterns of output neuron recruitment. This proposal aims to examine these non-binary signal transformations performed by interneuron microcircuits using striatal fast-spiking interneuron (FSI) microcircuits as a model system. We will utilize a novel pharmacological approach to separate the contribution of excitatory and inhibitory FSI inputs, hypothesizing that vector-conserved changes in excitation or inhibition will have non-overlapping effects on circuit output. Our objective is to reveal fundament properties of information processing by inhibitory microcircuits, providing a physiological model for the investigation and interpretation of microcircuit manipulations across neuronal systems.

Interneuron microcircuits integrate and transform afferent neurotransmission into broad effects on principal neuron output. This proposal aims to study this fundamental component of neurophysiology using striatal fast-spiking interneuron microcircuits as a model system. Using novel pharmacological and circuit-visualization approaches, we aim to establish causal relationships between excitatory and inhibitory microcircuit inputs to both striatal circuit output and the expression of habitual and compulsive behaviors.