The Projection From Ventral CA1, Not Prefrontal Cortex, to Nucleus Accumbens Core Mediates Recent Memory Retrieval of Cocaine-Conditioned Place Preference

Drug-paired cues inducing memory retrieval by expressing drug-seeking behaviors present a major challenge to drug abstinence. How neural circuits coordinate for drug memory retrieval remains unclear. Here, we report that exposure of the training chamber where cocaine-conditioned place preference (CPP) was performed increased neuronal activity in the core of nucleus accumbens (AcbC), ventral CA1 (vCA1), and medial prefrontal cortex (mPFC), as shown by elevated pERK and c-Fos levels. Chemogenetic inhibition of neuronal activity in the vCA1 and AcbC, but not mPFC, reduced the time spent in the cocaine-paired compartment, suggesting that the vCA1 and AcbC are required for the retrieval of cocaine-CPP memory and are key nodes recruited for cocaine memory storage. Furthermore, chemogenetic inhibition of the AcbC-projecting vCA1 neurons, but not the AcbC-projecting mPFC neurons, decreased the expression of cocaine-CPP. Optogenetic inhibition of the vCA1–AcbC projection, but not the mPFC–AcbC projection, also reduced the preference for the cocaine-paired compartment. Taken together, the cue-induced natural recall of cocaine memory depends on vCA1–AcbC circuits. The connectivity from the vCA1 to the AcbC may store the information of the cue–cocaine reward association critically required for memory retrieval. These data thus provide insights into the neural circuit basis of retrieval of drug-related memory.