ABSTRACT
Background The nucleus accumbens (NAc) controls multiple facets of impulsivity, but is a heterogeneous brain region with diverse microcircuitry. Prior literature links impulsive behavior in rodents to gamma aminobutyric acid (GABA) signaling in the NAc. Here, we studied the regulation of impulsive behavior by fast-spiking interneurons (FSIs), a strong source of GABAergic synaptic inhibition in the NAc.
Methods Male and female transgenic mice expressing Cre recombinase in FSIs allowed us identify these sparsely distributed cells in the NAc. We used the 5-choice serial reaction time (5-CSRT) task to measure both impulsive action and sustained attention. During the 5-CSRT task, we monitored FSI activity with fiber photometry calcium imaging, and manipulated FSI activity with chemogenetics. We used electrophysiology, optogenetics, and fluorescent in situ hybridization to confirm these methods were robust and specific to FSIs.
Results In mice performing the 5-CSRT task, NAc FSIs showed sustained activity on trials ending with correct responses. In contrast, FSI activity declined over time on trials ending with premature responses, as well as trials in which responses were omitted. Chemogenetic inhibition of NAc FSIs did not change response latencies or general locomotor activity, but significantly increased the number of premature responses, while the number of omission trials either remained constant or decreased.
Conclusions These experiments provide strong evidence that NAc FSIs constrain impulsive actions, most likely by GABA-mediated synaptic inhibition of medium spiny neuron output. Our findings may provide insight into the pathophysiology of impulse control disorders, and inform the development of circuit-based therapeutic interventions.
