Direct Reactivation of a Coherent Neocortical Memory of Context

Declarative memories are thought to be stored within anatomically distributed neuronal networks requiring the hippocampus; however, it is unclear how neocortical areas participate in memory at the time of encoding. Here, we use a c-fos-based genetic tagging system to selectively express the channelrhodopsin variant, ChEF, and optogenetically reactivate a specific neural ensemble in retrosplenial cortex (RSC) engaged by context fear conditioning. Artificial stimulation of RSC was sufficient to produce both context-specific behavior and downstream cellular activity commensurate with natural experience. Moreover, optogenetically but not contextually elicited responses were insensitive to hippocampal inactivation, suggesting that although the hippocampus is needed to coordinate activation by sensory cues, a higher-order cortical framework can independently subserve learned behavior, even shortly after learning. •Optogenetic stimulation of RSC reactivated a contextual fear memory•Both artificial and natural retrieval of memory activated common amygdala neurons•Artificial recall by RSC stimulation was unimpaired by hippocampal inactivation Cowansage et al. use a genetic system to optogenetically tag learning-activated neurons in retrosplenial cortex. Stimulation of these neurons induced behavior and brain activity similar to natural recall. Recall was hippocampus independent, suggesting cortical networks rapidly establish functional memory representations.