GABAergic interneurons expressing the α2 nicotinic receptor subunit are functionally integrated in the striatal microcircuit

The interactions between the striatal cholinergic and GABAergic systems are crucial in shaping reward-related behavior and reinforcement learning; however, the synaptic pathways mediating them are largely unknown. Here, we use Chrna2-Cre mice to characterize striatal interneurons (INs) expressing the nicotinic α2 receptor subunit. Using triple patch-clamp recordings combined with optogenetic stimulations, we characterize the electrophysiological, morphological, and synaptic properties of striatal Chrna2-INs. Striatal Chrna2-INs have diverse electrophysiological properties, distinct from their counterparts in other brain regions, including the hippocampus and neocortex. Unlike in other regions, most striatal Chrna2-INs are fast-spiking INs expressing parvalbumin. Striatal Chrna2-INs are intricately integrated in the striatal microcircuit, forming inhibitory synaptic connections with striatal projection neurons and INs, including other Chrna2-INs. They receive excitatory inputs from primary motor cortex mediated by both AMPA and NMDA receptors. A subpopulation of Chrna2-INs responds to nicotinic input, suggesting reciprocal interactions between this GABAergic interneuron population and striatal cholinergic synapses. [Display omitted] •Triple whole-cell recordings are used to study striatal interneurons in Chrna2-Cre mice•Unlike in other brain regions, most striatal Chrna2-interneurons express parvalbumin•Three distinct subtypes of striatal Chrna2-interneurons are defined•Their synaptic connectivity is mapped using optogenetics and patch-clamp recordings Tokarska and Silberberg characterize the cellular and circuit properties of striatal interneurons expressing Chrna2, the gene encoding for the nicotinic α2 receptor subunit. Using multineuron whole-cell recordings and optogenetic stimulations, they find that striatal Chrna2-interneurons form a diverse neuronal population that is distinct from Chrna2 neurons in other brain regions.