Principles of Synaptic Organization of GABAergic Interneurons in the Striatum

Abstract

The striatum, the entry nucleus of the basal ganglia, lacks laminar or columnar organization of its principal cells; nevertheless, functional data suggest that it is spatially organized. Here we examine whether the connectivity and synaptic organization of striatal GABAergic interneurons contributes tosuch spatial organization. Focusing on the twomain classes of striatal GABAergic interneurons (fast-spiking interneurons [FSIs] and low-threshold-spiking interneurons [LTSIs]), we apply a combination of optogenetics and viral tracing approaches to dissect striatal microcircuits in mice. Our results reveal fundamental differences between the synaptic organizations of both interneuron types. FSIs target exclusively striatal projection neurons (SPNs) within close proximity and form strong synapses on theproximal somatodendritic region. In contrast, LTSIs target both SPNs and cholinergic interneurons, and synaptic connections onto SPNs are made exclusively over long distances and onto distaldendrites. These results suggest fundamentally different functions of FSIs and LTSIs in shaping striatal output.