Molecular Mechanisms of the Memory Trace

Abstract

Over the past half-century, we have gained significant insights into the molecular biology of long-term memory storage at the level of the synapse. In recent years, our understanding of the cellular architecture supporting long-term memory traces has also substantially improved. However, the molecular biology of consolidation at the level of neuronal systems has been relatively neglected. In this opinion article, we first examine our current understanding of the cellular mechanisms of synaptic consolidation. We then outline areas requiring further investigation on how cellular changes contribute to systems consolidation. Finally, we highlight recent findings on the cellular architecture of memory traces in rodents and how the application of new technologies will expand our understanding of systems consolidation at the neural circuit level. In the coming years, this research focus will be critical for understanding the evolution of long-term memories and for enabling the development of novel therapeutics which embrace the dynamic nature of memories.

Induction of activity synchronization among primed hippocampal neurons out of random dynamics is key for trace memory formation and retrieval

“…It is generally thought that intensive neuronal stimulation induces short-term synaptic plasticity and the early phase of long-term potentiation (LTP), 39,62 which is followed by the late phase LTP for long-term memory consolidation. 39,63 The late-phase LTP is enabled by activity-induced calcium entry via the calcium-cAMP-MAPK-CREB pathway. 40,[63][64][65] Consequently, the nuclei of memory-eligible neurons receive a signal to initiate gene transcription and protein translation.…”

“…39,63 The late-phase LTP is enabled by activity-induced calcium entry via the calcium-cAMP-MAPK-CREB pathway. 40,[63][64][65] Consequently, the nuclei of memory-eligible neurons receive a signal to initiate gene transcription and protein translation. 40,63 Newly synthesized proteins are then delivered to the potentiated synapses, consolidating the tentatively potentiated synaptic efficacy for memory consolidation.…”

“…40,[63][64][65] Consequently, the nuclei of memory-eligible neurons receive a signal to initiate gene transcription and protein translation. 40,63 Newly synthesized proteins are then delivered to the potentiated synapses, consolidating the tentatively potentiated synaptic efficacy for memory consolidation. 39,40 Hence, very likely the synchronization-facilitated robust calcium entry will promote memory consolidation.…”

The Distributed Engram

“…Some of these processes take part as the neural and molecular basis of behavior, in addition to learning (25)(26)(27)(28)(29) . Thirdly, neurons interact by exploiting dozens of neuromodulators, neuropeptides, diffusible molecules, hormones and RNA, whose effect is not restricted to learning (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41) . Synaptic weights and electric currents, in these cases, are only part of a broader mechanism, and are not sufficient for memory induction, storage and expression.…”

microRNA mir-598-3p mediates susceptibility to stress-enhancement of remote fear memory

“…Persistent, maladaptive long-term memories are an integral part of several psychiatric disorders, including substance use disorder (SUD, [1]) and post-traumatic stress disorder (PTSD, [2]). While much of the current literature has focused on mechanisms supporting recent memory acquisition and consolidation [3], a greater understanding of the neurobiological mechanisms governing persistent, enhanced remote memory could provide new insight into treatment of memory-related disorders. Additionally, memories that drive unwanted flashbacks of trauma in PTSD are unique from normal episodic memories in that they are intrusive and more life-like in nature [4].…”