Key result
Chemogenetic reduction of hyperactive premotor corticostriatal activity rescues alcohol-impaired goal-directed action control in mice.
Why the study?
Alcohol use disorder alters decision-making control over actions, but whether there is a causal link between disrupted premotor corticostriatal activity and altered action control was unknown.
Does chemogenetic reduction of M2-DMS neuron hyperactivity improve goal-directed action control in mice chronically exposed to alcohol?
Does chemogenetic reduction of M2-DMS neuron hyperactivity improve goal-directed action control in mice chronically exposed to alcohol?
Chemogenetic reduction of hyperactive premotor corticostriatal circuits rescues goal-directed action control in mice chronically exposed to alcohol, suggesting a potential therapeutic target for alcohol use disorder.
May identify premotor corticostriatal hyperactivity as an AUD target; leaves open human translation.
Alcohol use disorder (AUD) alters decision-making control over actions, but disruptions to the responsible neural circuit mechanisms are unclear. Premotor corticostriatal circuits are implicated in balancing goal-directed and habitual control over actions and show disruption in disorders with compulsive, inflexible behaviors, including AUD. However, whether there is a causal link between disrupted premotor activity and altered action control is unknown. Here, we find that mice chronically exposed to alcohol (chronic intermittent ethanol [CIE]) showed impaired ability to use recent action information to guide subsequent actions. Prior CIE exposure resulted in aberrant increases in the calcium activity of premotor cortex (M2) neurons that project to the dorsal medial striatum (M2-DMS) during action control. Chemogenetic reduction of this CIE-induced hyperactivity in M2-DMS neurons rescued goal-directed action control. This suggests a direct, causal relationship between chronic alcohol disruption to premotor circuits and decision-making strategy and provides mechanistic support for targeting activity of human premotor regions as a potential treatment in AUD.
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Schreiner et al. (2023) studied Alcohol use disorder. Chronic intermittent ethanol (CIE) exposure was evaluated on Goal-directed action control and calcium activity of M2-DMS neurons. In mice, chronic alcohol exposure impaired goal-directed action control via hyperactive premotor corticostriatal activity, which was rescued by chemogenetic reduction of this hyperactivity.
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