Optogenetic Dissection of the Striatal Microcircuitry

Abstract

The striatum is the principal input structure of the basal ganglia, comprised almost entirely of inhibitory neurons, which include projection neurons and a small yet diverse population of interneurons. Striatal afferents include glutamatergic inputs from the neocortex and thalamus, and massive dopaminergic input from the substantia nigra pars compacta. In order to better understand the operational roles of striatum, it is essential to have a good grasp of its microcircuitry, namely a detailed description of its neuron types and their synaptic connectivity. Traditionally, studying synaptic connectivity between identified neurons was performed using paired and multineuron intracellular recordings in brain slices. The recent introduction of optogenetic methods offers new experimental approaches for microcircuit analysis, one of which is the combination of whole-cell patch-clamp recordings and optogenetic activation of presynaptic neurons. In this chapter we present recent advances in our understanding of the striatal microcircuitry when studied with electrophysiological and optogenetic methods. We first introduce the different neuron types comprising the striatal microcircuitry and describe their basic interconnectivity as inferred from electrophysiological measurements. We then present a few recent studies performed primarily in striatal and corticostriatal slices, where the powerful combination of electrophysiology and optogenetics revised our understanding of striatal functional organization.