Memory Storage in Distributed Engram Cell Ensembles.

One of the most fascinating aspects of the brain is its ability to acquire new information from experience and retain it over time as memory. The search for physical correlates of memory, the memory engram, has been a longstanding priority in modern neurobiology. Advanced genetic approaches have led to the localization of engram cells in a few brain regions, including the hippocampus and cortex. Additionally, engram cells exhibit learning-induced, persistent modifications and have at least two states, active and silent. However, it has been hypothesized that engrams for a specific memory are distributed among multiple brain regions that are functionally connected, referred to as a unified engram complex. Recent tissue-clearing techniques have permitted high-throughput analyses of intact brain samples, which have been used to obtain a map of the engram complex for a contextual fear memory. Careful examination of these engram complex maps has revealed a potentially underappreciated contribution of subcortical regions, specifically thalamic nuclei, to memory function. These more holistic studies support the unified engram complex hypothesis for memory storage and have important implications for understanding dysfunctional engrams in the context of human disease.