Engram Reactivation Mimics Cellular Signatures of Fear

Summary Engrams, or the physical substrate of memory in the brain, recruit heterogeneous cell-types. Targeted reactivation of neurons processing discrete memories drives the behavioral expression of memory, though the underlying landscape of recruited cells and their real-time responses remain elusive. To understand how artificial stimulation of fear affects intra-hippocampal neuronal and astrocytic dynamics as well as their behavioral consequences, we expressed channelrhodopsin-2 in an activity-dependent manner in dentate gyrus neurons while performing fiber photometry of both cell types in ventral CA1 across learning and memory. Neurons and astrocytes were shock-responsive, while astrocytic calcium events were uniquely modulated by fear conditioning. Notably, optogenetic stimulation of a hippocampus-mediated engram recapitulated coordinated calcium signatures time-locked to freezing that were also observed during natural fear memory recall, suggesting that engram activation alters activity across different cell types within hippocampal circuits during the behavioral expression of fear. Together, our data reveals cell-type specific hippocampal dynamics during freezing behavior and points to neuronal-astrocytic coupling as a shared mechanism enabling the natural and artificial recall of a memory. Highlights Ventral hippocampal neurons and astrocytes are active during foot shock Calcium activity is time-locked to freezing during fear conditioning and recall Optogenetic reactivation of fear recapitulates cellular signatures seen during recall Reactivation of a fear memory allows prediction of freezing behavior