Molecular correlates of cocaine-associated learning in striatal Arc ensembles
Marine Salery, Instructor
Nestler Lab, Friedman Brain Institute
Icahn School of Medicine at Mount Sinai, New York

Abstract
Learned associations between the rewarding effects of drugs and the context in which they are experienced are decisive for precipitated drug-seeking and relapse. Emerging evidence suggests that drug-recruited neuronal ensembles represent a critical cellular substrate for the encoding of these associative memories. Here, we explore the dynamics and molecular mechanisms of both the recruitment of these ensembles upon initial drug exposure and their contribution to the encoding, strengthening and ultimately expression of drug-context associations. Capitalizing on the activity-dependent labeling in Arc-CreERT2 mice, we captured and permanently tagged cocaine-activated cells in the Nucleus Accumbens. We show that distinct ensembles are recruited at early versus late stages of cocaine-context conditioning and that their reactivation during context re-exposure correlates with memory strength. Using optogenetic-mediated artificial reactivation, we found that these distinct populations had opposing roles in memory recall. Using single nucleus RNA-Sequencing, we identified intrinsic and acquired cellular properties favoring the allocation of specific cells to these ensembles and predicting their further reactivation. Together, this ensemble-specific approach represents a pivotal step in identifying highly specific cellular processes involved in the encoding of pathological memories associated with drug addiction.

Invited by Rosa Cossart
Wednesday December 20th at 11 am – Inmed conference room