Publication Date

7-1-2025

Journal

Nature Neuroscience

DOI

10.1038/s41593-025-01930-5

PMID

40169932

PMCID

PMC12229891

PubMedCentral® Posted Date

4-1-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Hippocampal CA1 place cells (PCs) encode both space- and goal-referenced information to support a cognitive map. The mechanism of this referencing and the role of experience remain poorly understood. Here we longitudinally recorded PC activity while head-fixed mice performed a spatial learning task on a treadmill. In a familiar environment, the CA1 representation consisted of PCs that were referenced to either specific spatial locations or a reward goal in approximately equal proportions; however, the CA1 representation became predominately goal-referenced upon exposure to a novel environment, as space-referenced PCs adaptively switched reference frames. Intracellular membrane potential recordings revealed that individual CA1 neurons simultaneously received both space- and goal-referenced synaptic inputs, and the ratio of these inputs was correlated with individual PC referencing. Furthermore, behavioral timescale synaptic plasticity shaped PC referencing. Together, these results suggest that experience-dependent adjustment of synaptic input shapes PC referencing to support a flexible cognitive map.

Keywords

Animals, CA1 Region, Hippocampal, Mice, Place Cells, Male, Mice, Inbred C57BL, Neuronal Plasticity, Spatial Learning, Reward, Long-term potentiation, Hippocampus, Reward

Published Open-Access

yes

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