Prior Cocaine Use Alters the Normal Evolution of Information Coding in Striatal Ensembles during Value-Guided...

Area of Science:

• Neuroscience
• Behavioral Science
• Addiction Research

Background:

• Substance use disorders (SUDs) involve maladaptive behaviors potentially linked to impaired environmental state encoding.
• The dorsomedial striatum (DMS) is crucial for behavioral flexibility and state encoding, suggesting its role in SUDs.
• Drug-induced neural alterations may disrupt state encoding, contributing to the maladaptive behaviors seen in SUDs.

Purpose of the Study:

• To investigate how prior cocaine exposure affects state and state-related information encoding in the DMS.
• To determine if DMS neural activity in cocaine-experienced rats differs during a decision-making task with distinct environmental states.

Main Methods:

• Recorded DMS neural activity in male rats with prior cocaine or sucrose experience during a state-based decision-making task.
• Analyzed medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) for encoding of trial-specific rules (response direction, value).

Main Results:

• DMS MSNs and FSIs encoded state-specific information and rules.
• Cocaine-experienced rats showed higher classification accuracy of trial-specific rules in DMS neurons compared to sucrose-experienced rats.
• Overly strengthened rule representations in cocaine-experienced rats correlated with slower switching behavior and reaction times.

Conclusions:

• Prior cocaine exposure paradoxically enhances the encoding of state-specific information and rules in the DMS.
• Abnormally specific and persistent rule representations in the DMS may slow value-based decision-making.
• This over-encoding mechanism in the DMS could underlie maladaptive behaviors observed in substance use disorders.