Chronic nicotine impairs sparse motor learning via striatal fast‐spiking parvalbumin interneurons

Abstract

Nicotine can diversely affect neural activity and motor learning in animals. However, the impact of chronic nicotine on striatal activity in vivo and motor learning at long‐term sparse timescale remains unknown. Here, we demonstrate that chronic nicotine persistently suppresses the activity of striatal fast‐spiking parvalbumin interneurons, which mediate nicotine‐induced deficit in sparse motor learning. Six weeks of longitudinal in vivo single‐unit recording revealed that mice show reduced activity of fast‐spiking interneurons in the dorsal striatum during chronic nicotine exposure and withdrawal. The reduced firing of fast‐spiking interneurons was accompanied by spike broadening, diminished striatal delta oscillation power, and reduced sample entropy in local field potential. In addition, chronic nicotine withdrawal impaired motor learning with a weekly sparse training regimen but did not affect general locomotion and anxiety‐like behavior. Lastly, the excitatory DREADD hM3Dq‐mediated activation of striatal fast‐spiking parvalbumin interneurons reversed the chronic nicotine withdrawal‐induced deficit in sparse motor learning. Taken together, we identified that chronic nicotine withdrawal impairs sparse motor learning via disruption of activity in striatal fast‐spiking parvalbumin interneurons. These findings suggest that sparse motor learning paradigm can reveal the subtle effect of nicotine withdrawal on motor function and that striatal fast‐spiking parvalbumin interneurons are a neural substrate of nicotine's effect on motor learning.

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“…The within-group, learning-mediated enhancement in motor skill (motor learning index) was calculated according to the previous study 18 . The motor learning index was defined as the average of latency to fall within a session normalized to the average of the latency to fall in the first session, expressed in percentage.…”