Engram dynamics under memory consolidation
File(s)
Author(s)
Feitosa Tomé, Douglas
Type
Thesis
Abstract
Engram refers to the physical and chemical changes in the brain thought to encode memories of specific events. Recent technological advancements have enabled the identification and manipulation of engram cells, leading to breakthroughs in memory research. In particular, engram cells in distributed brain regions have been shown to evolve in distinct ways over the course of systems consolidation but the underlying mechanisms remain unknown. Also, numerous studies have reported that only a small fraction of training-activated engram cells is reactivated during recall, raising the possibility that the neural composition of engrams may be dynamic. Furthermore, distinct molecularly-defined neuronal ensembles within an engram have been identified but their temporal evolution remains elusive. Here we investigated how engrams evolve with memory consolidation across multiple spatiotemporal scales. We used a computational model to explore the mechanisms behind long-term engram dynamics under systems consolidation. By incorporating a hippocampus-thalamus-cortex circuit with coordinated synaptic plasticity timescales, our model exhibited coupled engram reactivations that led to region-specific changes in the retrievability of engram cells. We also employed a computational model to probe the short-term evolution of the composition and selectivity of hippocampal engrams. Our modeling results predicted that engrams are dynamic and become selective over the course of memory consolidation, with inhibition and inhibitory synaptic plasticity being fundamental for memory selectivity. Contextual fear conditioning experiments have supported these predictions. Moreover, we used a computational model to examine the temporal evolution of engram cells expressing either the immediate-early gene Fos or Npas4. Our results suggested that Fos- and Npas4-expressing engram cell ensembles evolve in different ways but both become selective with memory consolidation. Overall, our work suggests that the retrievability, neural composition, and selectivity of engrams are fluid — pointing to distributed, dynamic, and heterogeneous engrams as the neural substrate of memory formation, consolidation, and retrieval.
Version
Open Access
Date Issued
2022-02
Date Awarded
2022-04
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Clopath, Claudia
Sponsor
Imperial College London
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)