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bioRxiv · 10.1101/2021.09.02.458796

Neural circuit dynamics of drug-context associative learning in the hippocampus

Sun, Y.·Giocomo, L. M.
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Abstract

The environmental context associated with previous drug consumption serves as a potent trigger for relapse to drug use. The mechanism by which existing neural representations of context are modified to incorporate information associated with a given drug however, remains unknown. Using longitudinal calcium imaging in freely behaving mice, we reveal that drug-context associations for psychostimulants and opioids are encoded in a subset of hippocampal neurons. In these neurons, drug context pairing in a conditioned place preference task weakened their spatial coding for the nondrug-paired context, with drug-induced changes to spatial coding predictive of drug-seeking behavior. Furthermore, the dissociative drug ketamine blocked both the drug-induced changes to hippocampal coding and corresponding drug-seeking behavior. Together, this work reveals how drugs of abuse can alter the hippocampal circuit to encode drug-context associations and points to the hippocampus as a key node in the cognitive process of drug addiction and context-induced drug relapse.

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Sun, Y., Giocomo, L. M.. 2021-09-05. Neural circuit dynamics of drug-context associative learning in the hippocampus. https://doi.org/10.1101/2021.09.02.458796

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