Language

English

Publication Date

7-1-2025

Journal

Nature Neuroscience

DOI

10.1038/s41593-025-01986-3

PMID

40467863

PMCID

PMC12229897

PubMedCentral® Posted Date

6-4-2025

PubMedCentral® Full Text Version

Post-print

Abstract

How brain networks connected by labile synapses store new information without catastrophically overwriting previous memories remains poorly understood. To examine this, we tracked the same population of hippocampal CA1 place cells (PCs) as mice learned a task for 7 days. We found evidence of memory formation as both the number of PCs maintaining a stable place field and the stability of individual PCs progressively increased across the week until most of the representation was composed of long-term stable PCs. The stable PCs disproportionately represented task-related learned information, were retrieved earlier within a behavioral session and showed a strong correlation with behavioral performance. Both the initial formation of PCs and their retrieval on subsequent days were accompanied by prominent signs of behavioral timescale synaptic plasticity (BTSP), suggesting that even stable PCs were re-formed by synaptic plasticity each session. Further experimental evidence supported by a cascade-type state model indicates that CA1 PCs increase their stability each day they are active, eventually forming a highly stable population. The results suggest that CA1 memory is implemented by an increase in the likelihood of new neuron-specific synaptic plasticity, as opposed to extensive long-term synaptic weight stabilization.

Keywords

Animals, Mice, Neuronal Plasticity, Memory, CA1 Region, Hippocampal, Male, Mice, Inbred C57BL, Hippocampus, Place Cells, Hippocampus, Long-term memory

Published Open-Access

yes

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