RT Journal Article SR Electronic T1 Engram Stability and Maturation During Systems Consolidation Underlies Remote Memory JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.07.31.502182 DO 10.1101/2022.07.31.502182 A1 Ron Refaeli A1 Tirzah Kreisel A1 Maya Groysman A1 Adar Adamsky A1 Inbal Goshen YR 2022 UL http://biorxiv.org/content/early/2022/08/02/2022.07.31.502182.abstract AB Remote memories play an important role in how we perceive the world and are rooted in ensembles in the CA1 and ACC, however the evolution of these components during systems consolidation has not yet been comprehensively addressed. By applying transgenic approaches for ensemble identification, CLARITY, retro-AAV and rabies virus for circuit mapping, and chemogenetics for functional interrogation, we addressed the dynamics of CA1-ACC ensembles and their connectivity as well as the contribution of astrocytes to the process. We found that the CA1 engrams remain stable between recent and remote recall, and, the inhibition of the engram for recent recall during remote recall functionally impairs memory. We also found that the new cells in the remote recall engram in the CA1 are not added randomly, but differ according to their connections: First, the anterograde CA1 → ACC engram cell projection grows larger. Second, in the retrograde projections, the ACC reduces input to CA1 engram cells, while input from the entorhinal cortex and paraventricular nucleus of the thalamus increases. Finally, we found that activating CA1 astrocytes during acquisition improves recent but not remote recall, and that CA1 → ACC projecting cells are recruited earlier when the astrocytes are stimulated. Our results shine fresh light on systems consolidation by providing a deeper understanding of engram stability and maturation in the transition from recent to remote memory.Competing Interest StatementThe authors have declared no competing interest.