PT  - JOURNAL ARTICLE
AU  - Yanjun Sun
AU  - Lisa M Giocomo
TI  - Neural circuit dynamics of drug-context associative learning in the hippocampus
AID  - 10.1101/2021.09.02.458796
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.09.02.458796
4099  - http://biorxiv.org/content/early/2021/09/05/2021.09.02.458796.short
4100  - http://biorxiv.org/content/early/2021/09/05/2021.09.02.458796.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.