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

• Published in: Nature communications Vol. 13; no. 1; pp. 6721 - 19
• Main Authors: Sun, Yanjun, Giocomo, Lisa M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.11.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 631/378/1595/1554; 631/378/3920; Animals; Associative learning; Calcium imaging; Circuits; Conditioning, Classical; Context; Drug abuse; Drug addiction; Drug-Seeking Behavior; Drugs; Hippocampus; Hippocampus - physiology; Humanities and Social Sciences; Learning; Methamphetamine; Mice; multidisciplinary; Narcotics; Neural coding; Neurons; Neurons - physiology; Neurosciences; Reinforcement; Representations; Reward; Science; Science (multidisciplinary); Substance use
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34114-x

The environmental context associated with previous drug consumption is a potent trigger for drug relapse. However, the mechanism by which neural representations of context are modified to incorporate information associated with drugs of abuse remains unknown. Using longitudinal calcium imaging in freely behaving mice, we find that unlike the associative learning of natural reward, drug-context associations for psychostimulants and opioids are encoded in a specific subset of hippocampal neurons. After drug conditioning, these neurons weakened their spatial coding for the non-drug paired context, resulting in an orthogonal representation for the drug versus non-drug context that was predictive of drug-seeking behavior. Furthermore, these neurons were selected based on drug-spatial experience and were exclusively tuned to animals’ allocentric position. Together, this work reveals how drugs of abuse alter the hippocampal circuit to encode drug-context associations and points to the possibility of targeting drug-associated memory in the hippocampus. Drug-associated contexts are a strong trigger for relapse to substance use. Here, the authors report that a subpopulation of neurons in the hippocampus of mice specifically encode drug-associated contextual information.