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• W3101476051 abstract "Substance use disorders (SUDs) are characterized by maladaptive behavior. The ability to properly adjust behavior according to changes in environmental contingencies necessitates the interlacing of existing memories with updated information. This can be achieved by assigning learning in different contexts to compartmentalized “states.” Though not often framed this way, the maladaptive behavior observed in individuals with SUDs may result from a failure to properly encode states because of drug-induced neural alterations. Previous studies found that the dorsomedial striatum (DMS) is important for behavioral flexibility and state encoding, suggesting the DMS may be an important substrate for these effects. Here, we recorded DMS neural activity in cocaine-experienced male rats during a decision-making task where blocks of trials represented distinct states to probe whether the encoding of state and state-related information is affected by prior drug exposure. We found that DMS medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) encoded such information and that prior cocaine experience disrupted the evolution of representations both within trials and across recording sessions. Specifically, DMS MSNs and FSIs from cocaine-experienced rats demonstrated higher classification accuracy of trial-specific rules, defined by response direction and value, compared with those drawn from sucrose-experienced rats, and these overly strengthened trial-type representations were related to slower switching behavior and reaction times. These data show that prior cocaine experience paradoxically increases the encoding of state-specific information and rules in the DMS and suggest a model in which abnormally specific and persistent representation of rules throughout trials in DMS slows value-based decision-making in well trained subjects. SIGNIFICANCE STATEMENT Substance use disorders (SUDs) may result from a failure to properly encode rules guiding situationally appropriate behavior. The dorsomedial striatum (DMS) is thought to be important for such behavioral flexibility and encoding that defines the situation or “state.” This suggests that the DMS may be an important substrate for the maladaptive behavior observed in SUDs. In the current study, we show that prior cocaine experience results in over-encoding of state-specific information and rules in the DMS, which may impair normal adaptive decision-making in the task, akin to what is observed in SUDs." @default.
• W3101476051 created "2020-11-23" @default.
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• W3101476051 date "2020-11-20" @default.
• W3101476051 modified "2023-10-02" @default.
• W3101476051 title "Prior Cocaine Use Alters the Normal Evolution of Information Coding in Striatal Ensembles during Value-Guided Decision-Making" @default.
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• W3101476051 doi "https://doi.org/10.1523/jneurosci.1755-20.2020" @default.
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