Memory engrams: Recalling the past and imagining the future

Abstract

In 1904, Richard Semon introduced the term “engram” to describe the neural substrate for storing memories. An experience, Semon proposed, activates a subset of cells that undergo off-line, persistent chemical and/or physical changes to become an engram. Subsequent reactivation of this engram induces memory retrieval. Although Semon’s contributions were largely ignored in his lifetime, new technologies that allow researchers to image and manipulate the brain at the level of individual neurons has reinvigorated engram research. We review recent progress in studying engrams, including an evaluation of evidence for the existence of engrams, the importance of intrinsic excitability and synaptic plasticity in engrams, and the lifetime of an engram. Together, these findings are beginning to define an engram as the basic unit of memory.

PKA drives an increase in AMPA receptor unitary conductance during LTP in the hippocampus

“…Long-term potentiation (LTP) of synaptic function is considered the major process underlying learning and memory 1 where it is involved in synaptic engram formation 2,3 , yet the underlying cellular mechanisms remain incompletely understood. The best-characterized form of LTP occurs at the Schaffer collateral-commissural pathway (SCCP) in the hippocampus, where it is triggered by synaptic activation of NMDA (N-methyl-D-aspartate) receptors 4 and is expressed as a persistent increase in AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor-mediated synaptic transmission 5 .…”

Principles for coding associative memories in a compact neural network

“…To synthesize a productive associative memory that elicits an adaptive response upon future encounter with the CS, both the CS and the US must be encoded in the neural system. Moreover, their encoding needs to be logically integrated such that the behavioral response will match the expected valence that the CS predicts (Josselyn and Tonegawa, 2020) .…”

“…In contrast, mammalian brains are thought to encode associative memories in a decentralized fashion where interconnected areas, distributed throughout the entire brain, link up to encode memory traces. For example, associative fear memories are thought to be distributed among the amygdala that encodes the valence , the hippocampus which encodes the context, and the cortical neurons which provide the specific sensory information (Josselyn and Tonegawa, 2020) . Furthermore, sensory neurons proved to play intriguing roles in formation of associative memories.…”

Latent learning drives sleep-dependent plasticity in distinct CA1 subpopulations

“…Recent studies showed that hippocampal neurons also encode a wide range of non-spatial information that enables cognitive functions beyond spatial navigation 3–6 . However, we still lack a clear understanding of how cognitive maps emerge during learning 2,7–9 . By studying subjects performing foraging or reinforcement learning tasks, we limited ourselves in observing neural activities associated with overt behavioral changes, whereas cognitive maps can be acquired and stored implicitly.…”

“…We provided a mechanism showing how a cognitive map can be built via latent learning and stored as a neural manifold. Although we only investigated simple 2D spatial exploration experiences, with our framework, non-spatial information such as sensory cues, reward, behavioral states, and even the concept of time can all be stored in same the manifold, likely in the other dimensions, providing a holistic, schema like representation of the animal’s experience 2,7–9,33 . Our work also showcased the often- neglected WS cells in the HPC, demonstrating the importance of understanding heterogeneity in the HPC neurons 34,35 .…”