Formation of Hippocampal Memory Engrams by Ensemble Allocation and their Role in Context-dependent Modulation of Hippocampal Output during Memory Recall
Year: 2024
Type: dissertation
Abstract: Memory endows animals with the ability to store information from past experience to optimize future behaviour for survival and reproduction. A century of work has gradually improved the precision with which one can localize a particular memory to physical changes or components in the brain, from whole brain regions to specific sets of cells or synapses. At the same time, the ability to precisely manipulate specific memories, while leaving others intact, has also improved. For hippocampus-dependent memories, a small subset of hippocampal neurons called an ‘engram’ are recruited to store any particular memory. The likelihood that any given neuron is allocated to a memory’s engram is strongly influenced by the excitability of the cell at the time of learning, however the role of other factors in allocation is not clear. We show that in the days prior to learning, many ensembles of neurons fluctuate in average activity levels, and the ensembles that are highly active on the day of training are preferentially allocated to the engram. Learning is accompanied by selective plasticity in the pattern of functional connectivity between engram neurons, and this structure is reinstated during memory recall. We then go on to generalize the engram concept to multi-trial learning of multiple associations formed in multiple contexts. In this case, all associations learned in a particular context are linked to the engram formed during the initial context exposure, such that activating the engram of a tagged context is sufficient to reverse memory-guided behaviour in a non-tagged context. Furthermore, engram stimulation is associated with the reinstatement of tagged-context ensemble activity in downstream hippocampal networks. The data presented in this thesis suggest a model of hippocampal memory whereby excitability determines which ensembles are recruited to encode a memory upon initial experience in a particular context, and subsequent visits to the encoding context render the underlying engram transiently excitable, and therefore labile tomodification by synaptic plasticity. Furthermore, we present evidence that temporally-blunt engram stimulation recruits endogenous patterns of activity to promote complex, memory-guided behaviour.
Source: TSpace (University of Toronto)
Author: Mocle, Andrew
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7133018632