Crystallizing a memory

What is the physical basis of memory? What does it take to retrieve a memory in the brain? What would it take to activate or erase memories? In the early 20th century, the German zoologist Richard Semon coined the term “engram” to denote the physical manifestation of a memory in the brain ( 1 ). Two decades later, Canadian psychologist Donald Hebb posited a physiological correlate for learning and recollection: The process of learning strengthens the connections, or synapses, between neurons, which leads to the development of brain-wide cell assemblies that undergo changes in their structural and functional connectivity ( 2 ). The coordinated activity of these assemblies—called ensembles, traces, or engrams—that occurs during learning (memory formation) is thought to be reengaged during recall and thereby forms a stable neuronal correlate of memory ( 2 ). As subsequent memories are formed, the dynamics of these assemblies evolve and provide preexisting scaffolds to influence how the brain processes the variety of memories an organism forms. Studies by Abdou et al. ( 3 ) on page 1227 of this issue and by Choi et al. ( 4 ) develop new technologies to visualize discrete engrams in the brain and modulate them in a synapse-specific manner to understand memory strength and memory restoration from an amnestic state. This improved understanding could eventually be translated to modulate memories to alleviate maladaptive memory states.