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Cavallaro, J.

Publications and source records attributed to Cavallaro, J..

2 recordsLinked to original sources

Nucleus accumbens acetylcholine dips track reward value and temporal costs to shape delay discounting

As an organism chooses between competing rewards, it must often integrate learned reward value with the changing costs associated with obtaining them. Yet, the brain mechanisms through which these factors jointly guide choice are not well understood. Previous studies have shown that dopamine signals in the nucleus accumbens (NAc) track reward value and are modulated by their associated delay costs. Our prior work further implicated NAc cholinergic interneurons by demonstrating that dopamine D2 receptors in these neurons influence choice under temporal, but not probabilistic, costs. However, whether NAc acetylcholine (ACh) dynamics track reward value and/or delay, and whether they contribute to adaptive choice, remains unknown. Using in vivo fiber photometry during a delay discounting task in which mice choose between a small, immediate reward and a larger, delayed reward, we reveal that cue-evoked ACh dips dynamically track relative reward magnitude and are diminished by increasing delays. Our data further show that optogenetically enhancing these dips attenuates the delay-dependent decline in choice of the larger, delayed reward. These findings identify a previously unrecognized role for NAc cue-evoked ACh dips in shaping adaptive choice as temporal costs increase.

neuroscience↗

Dopamine D2 receptors in nucleus accumbens cholinergic interneurons increase impulsive choice

Impulsive choice, often characterized by excessive preference for small, short-term rewards over larger, long-term rewards, is a prominent feature of substance use and other neuropsychiatric disorders. The neural mechanisms underlying impulsive choice are not well understood, but growing evidence implicates nucleus accumbens (NAc) dopamine and its actions on dopamine D2 receptors (D2Rs). Because several NAc cell types and afferents express D2Rs, it has been difficult to determine the specific neural mechanisms linking NAc D2Rs to impulsive choice. Of these cell types, cholinergic interneurons (CINs) of the NAc, which express D2Rs, have emerged as key regulators of striatal output and local dopamine release. Despite these relevant functions, whether D2Rs expressed specifically in these neurons contribute to impulsive choice behavior is unknown. Here, we show that D2R upregulation in CINs of the mouse NAc increases impulsive choice as measured in a delay discounting task without affecting reward magnitude sensitivity or interval timing. Conversely, mice lacking D2Rs in CINs showed decreased delay discounting. Furthermore, CIN D2R manipulations did not affect probabilistic discounting, which measures a different form of impulsive choice. Together, these findings suggest that CIN D2Rs regulate impulsive decision-making involving delay costs, providing new insight into the mechanisms by which NAc dopamine influences impulsive behavior.

neuroscience↗