Neural circuit dynamics of drug-context associative learning in the mouse hippocampus
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 07, 2022
- Source ID
- 10.1038/s41467-022-34114-x
Entities
People
- Lisa M. Giocomo
- Yanjun Sun
Organizations
- James S. McDonnell Foundation
- National Institute on Drug Abuse
- Office of Naval Research
- Vallee Foundation