Resources
Authors & Affiliations
Ali Golbabaei, Sheena Josselyn, Paul Frankland
Abstract
Memories are known to initially depend on the hippocampus for their expression but become more dependent on the medial prefrontal cortex (mPFC) at remote time-points. Although the retrieval-induced activity of mPFC increases with time, it is unclear whether distinct mPFC projection-specific populations (PSPs) contribute to retrieval at different time points. Here, delineate how these distinct PSPs contribute to memory expression at recent vs. remote time-points. We virally labeled PSPs and examined the extent to which they are reactivated during recent vs. remote recall. Then, we used optogenetics to either reactivate or silence these PSPs to assess their contribution to the recall at different time-points. Our results indicate that distinct PSPs contribute differentially to recent vs remote recall. In particular, PSPs that target basal amygdala (BA) or lateral entorhinal cortex (LEC) contribute to recall at both time-points, while PSPs that target nucleus reuniens (NRe) or nucleus accumbens (NAc) contribute more to remote recall. Consistently, optogenetic manipulations revealed that the BA and LEC contribute to the retrieval of the memories at both time-points while the NRe and NAc contribute to the recall only at the remote time-point. Next, we hypothesized that changes in local connectivity of mPFC are responsible for the recruitment of PSPs. We found that the local mPFC ensemble is connected to BA and LEC PSPs at recent time-point but it only becomes connected to NAC and NRE PSPs at remote time-point. Together, our findings characterize how local and long-range connections of mPFC reorganize during the consolidation of fear memories.