Spatially restricted inhibition of cholinergic interneurons in the dorsolateral striatum encourages behavioral exploration. (14th February 2021)

• Record Type: Journal Article
• Authors: Amaya, Kenneth A.; Smith, Kyle S.
• Is Part Of: European journal of neuroscience. Volume 53:Number 8(2021)
• Page Start: 2567
• Page End: 2579
• Publication Date: 2021-02-14
• Subjects: basal ganglia -- DREADDs -- habit -- learning -- reward; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.15117
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: When pursuing desirable outcomes, one must make the decision between exploring possible actions to obtain those outcomes and exploiting known strategies to maximize efficiency. The dorsolateral striatum (DLS) has been extensively studied with respect to how actions can develop into habits and has also been implicated as an area involved in governing exploitative behavior. Surprisingly, prior work has shown that DLS cholinergic interneurons (ChIs) are not involved in the canonical habit formation function ascribed to the DLS but are instead modulators of behavioral flexibility after initial learning. To further probe this, we evaluated the role of DLS ChIs in behavioral exploration during a brief instrumental training experiment. Through designer receptors exclusively activated by designer drugs (DREADDs) in ChAT‐Cre rats, ChIs in the DLS were inhibited during specific phases of the experiment: instrumental training, free‐reward delivery, at both times, or never. Without ChI activity during instrumental training, animals biased their responding toward an "optimal" strategy while continuing to work efficiently. This effect was observed again when contingencies were removed as animals with ChIs offline during that phase, regardless of ChI inhibition previously, decreased responding more than animals with ChIs intact. These findings build upon a growing body of literature implicating ChIs in the striatum as gate‐keepers of behavioral flexibility and exploration. Abstract : Cholinergic interneurons (ChIs) of the dorsolateral striatum (DLS) were chemogenetically targeted and inhibited during an instrumental training experiment. Without ChI activity during training, animals biased responding toward an optimal action strategy. This effect was observed again when contingencies were removed as animals with ChIs offline, regardless of previous ChI inhibition, decreased responding. These findings further implicate striatal ChIs as gate‐keepers of behavioral flexibility.