Memories thread and unify our overall sense of being. With the accumulation of our knowledge about how memories are formed, consolidated, retrieved, and updated, neuroscience has reached a point where brain cells active during these discrete mnemonic processes can be identified and manipulated at rapid timescales. Here, I begin with historical studies that lead to contemporary theories on the physical basis of memory engrams. Then, I present our recent advances in memory research that combine transgenic and optogenetic approaches to reveal underlying neuronal substrates sufficient for activating mnemonic processes. Our studies’ conclusions are threefold: (1) a defined subset of hippocampus cells are sufficient to elicit the neuronal and behavioral expression of positive and negative memory recall, as well as sufficient to modify existing positive and negative memories; (2) the hippocampus contains genetically and anatomically segregated populations of cells processing fear or reward in a projection-specific manner; (3) and finally, artificially activated memories can be leveraged to acutely and chronically suppress psychiatric disease-related states. We propose that cells that show activity-dependent changes during learning construct a cellular basis for memory engrams and that directly activating these endogenous neuronal processes may be an effective means to correct maladaptive behaviors.
 Activating positive memory engrams suppresses depression-like behaviour
 Artificially Enhancing and Suppressing Hippocampus-Mediated Memories