Understanding how the brain encodes, stores, and uses information is a central goal of neuroscience. Many neuropsychiatric and neurodegenerative disorders, including autism spectrum disorder, post-traumatic stress disorder (PTSD), and Alzheimer’s disease, may arise from disrupted information processing. Thus, uncovering the neural mechanisms by which information is represented in the brain is not only key to understanding normal cognition but also essential for developing targeted therapeutic strategies.
Memory can be defined as the persistence of internal representations acquired through experience, and the capacity to reconstruct these representations across time. The enduring physical changes in the brain that encode such information are referred to as engrams. Although the idea of a physical memory trace can be traced back to ancient Greek philosophy, it was not formally articulated until 1904 when Richard Semon coined the term engram. Despite this long conceptual history, identifying the precise neural substrates of an engram has proven remarkably difficult, in part because memory is encoded across multiple levels; from epigenetic and synaptic modifications to coordinated patterns of neuronal ensemble activity.
Our laboratory seeks to understand how specific neurons are recruited, or allocated, to a given engram, and how membership within these neuronal ensembles may evolve with time, plasticity, or new learning. By combining molecular, imaging, and behavioral approaches in mice, we aim to link changes in neuronal excitability and network dynamics to the stability and flexibility of memory representations. In my lecture, I will describe our historic and recent findings toward mapping and manipulating memory engrams in the mammalian brain, and discuss their implications for understanding both healthy and disordered memory.