Abstract
Systems consolidation refers to the time-dependent reorganization of memory representations or engrams across brain regions. Despite recent advancements in unravelling this process, the exact mechanisms behind engram dynamics and the role of associated pathways remain largely unknown. Here we propose a biologically-plausible computational model to address this knowledge gap. By coordinating synaptic plasticity timescales and incorporating a hippocampus-thalamus-cortex circuit, our model is able to couple engram reactivations across these regions and thereby reproduce key dynamics of cortical and hippocampal engram cells along with their interdependencies. Decoupling hippocampal-thalamic-cortical activity disrupts systems consolidation. Critically, our model yields testable predictions regarding hippocampal and thalamic engram cells, inhibitory engrams, thalamic inhibitory input, and the effect of thalamocortical synaptic coupling on retrograde amnesia induced by hippocampal lesions. Overall, our results suggest that systems consolidation emerges from coupled reactivations of engram cells in distributed brain regions enabled by coordinated synaptic plasticity timescales in multisynaptic subcortical-cortical circuits.
Highlights
Systems consolidation refers to the time-dependent reorganization of memory representations or engrams across brain regions
Our modeling results yield the following experimentally-testable predictions: engram cells in mediodorsal thalamus (THL) are active in recent and remote recall and are crucial for the maturation of engram cells in CTX; engram cells in HPC and THL are crucial for coupling engram reactivations across HPC, THL, and CTX in consolidation periods; inhibitory engram cells have distinct region-specific dynamics with coupled reactivations; inhibitory input to THL is critical for CTX engram maturation; and THL → CTX synaptic coupling is predictive of CTX engram dynamics and the retrograde amnesia pattern induced by HPC damage— providing a unifying mechanistic account for reconciliation of HPC lesion studies
One of four non-overlapping random stimuli is presented to the network at a time either for training or testing (Fig. 1a), and the network is subject to an episodic memory task to investigate engram dynamics
Summary
Systems consolidation refers to the time-dependent reorganization of memory representations or engrams across brain regions. Our modeling results yield the following experimentally-testable predictions: engram cells in mediodorsal thalamus (THL) are active in recent and remote recall and are crucial for the maturation of engram cells in CTX; engram cells in HPC and THL are crucial for coupling engram reactivations across HPC, THL, and CTX in consolidation periods; inhibitory engram cells have distinct region-specific dynamics with coupled reactivations; inhibitory input to THL is critical for CTX engram maturation; and THL → CTX synaptic coupling is predictive of CTX engram dynamics and the retrograde amnesia pattern induced by HPC damage— providing a unifying mechanistic account for reconciliation of HPC lesion studies. Our results suggest that coordinated hippocampal-thalamic-cortical communication underlies engram dynamics subserving systems consolidation
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