Long-Term Memory Engrams From Development to Adulthood

Abstract

Memories formed in adulthood can last a lifetime, whereas those formed early in life are rapidly forgotten through a process known as infantile amnesia. In recent years, tremendous progress has been made in understanding the memory engram-the physical trace of a memory in the brain-and how it transforms as memories evolve from recent to remote. This review focuses on engram cells and examines their roles in memory encoding, consolidation, retrieval, and forgetting from development to adulthood. We concentrate on four key brain regions: the hippocampus, the retrosplenial cortex, the medial prefrontal cortex, and the anterior thalamic nuclei. We first focus on the adult brain, highlighting recent studies that reveal the distinct contributions of engram cells in each brain region, with particular emphasis on synaptic plasticity and memory consolidation. We then explore how coordinated activity across these regions supports long-term memory. In the second section, we review emerging knowledge of engram cells in the developing brain, examining how developmental differences in their functions contribute to infant memory generalization and infantile amnesia. Compared to adults, much less is known about how, or to what extent, early-life memories undergo consolidation. In the final section, we synthesize current knowledge of memory consolidation and retrieval in the adult brain with what is known about the development of the four brain regions we discuss. We then propose key directions for future research. In sum, this review brings together recent findings that deepen our understanding of the dynamic changes in memory engrams that underlie consolidation and long-term storage and explores how developmental differences may shape the maturation of memory processes.

Keywords: development; infantile amnesia; memory consolidation; memory engram; synaptic plasticity.

FIGURE 1

The roles of engram cells in memory encoding, consolidation, and retrieval in adulthood. Summary of recent findings about engram cells in the mPFC, RSC, ATN, and HPC. (A) Processes occurring during learning on day (D) 0. EC‐ and LC‐inputs to mPFC are critical for tagging engram cells. Dopaminergic (Ventral Tegmental Area), HPC, and ATN inputs to RSC are critical for learning. ATN exhibits increased activity, IEG expression, and excitatory synapse density. Structural long‐term potentiation (sLTP) is evident in the hippocampus. Activity in the subiculum‐RSC pathway and astrocyte‐mediated recruitment of mPFC‐projecting CA1 engram cells are important for later memory retrieval. (B) Memory consolidation in the hours following learning, including during sleep, involves sLTP in mPFC and coordinated activity between ATN and mPFC, ATN‐RSC and ATN‐HPC. Additionally, there is incorporation of new neurons into the HPC engram and sleep‐dependent changes in gene expression in HPC engram cells. (C) Recent memory retrieval on D1 after learning involves ATN‐mPFC, ATN‐RSC‐EC, and HPC‐RSC pathway activity, NMDAR activity in RSC, addition of new/clustered dendritic spines in hippocampal neurons, and preferential connections between HPC engram cells. (D) Remote memory retrieval occurring 7 days or more after learning involves the maturation of mPFC engram cells and recruitment of new mPFC neurons to the memory engram, changes in gene expression in mPFC engram cells and mPFC astrocytes, spine growth and clustering in RSC neurons, ATN‐mPFC and ATN‐RSC pathway activity, and enhanced engram‐non‐engram cell synaptic connectivity in the HPC.

FIGURE 2

The roles of engram cells in memory encoding, consolidation, and retrieval in development. Summary of recent findings on engram cells in the HPC and RSC based on experiments conducted in ~P17–P20 rodents. (A) During learning, RSC neurons have high spine density compared to adults, engrams are dense in the RSC and HPC, and GluN2B activity is required for learning. (B) During recent memory retrieval, RSC neurons still have high spine density compared to adults and HPC engrams are dense. (C) During remote memory recall, RSC neurons still have higher spine density than adults, RSC engrams are unstable (infrequent reactivation of original engram cells), and HPC and RSC engrams are silent.