Dendrite-targeting OLM interneurons regulate the formation of learning-related CA1 place cell representations.

ABSTRACT: Spatial learning depends on the rapid formation of hippocampal CA1 place cell representations through behavioral timescale synaptic plasticity (BTSP)^1-7. BTSP is driven by dendritic Ca²⁺ plateau potentials in the distal apical dendrites of CA1 pyramidal neurons and is thought to arise from the interaction of an excitatory target signal from entorhinal cortex layer 3 (EC3) with inhibitory feedback reflecting the current CA1 population state8. However, the cellular source of this feedback remains unknown. To identify this circuit element, we combined in vivo two-photon calcium imaging with bidirectional optogenetic manipulation to examine the role of dendrite-targeting oriens lacunosum-moleculare (OLM) interneurons^9,10. We found that axonal and somatic activity of OLM interneurons increased with learning and was spatially biased toward behaviorally salient locations, closely matching the evolving CA1 population representation and the environment-specific EC3 target signal3. Causal manipulations revealed that optogenetic silencing of Chrna2α-positive OLM interneurons, a genetically defined OLM subset, late in learning increased dendritic plateaus and promoted place cell formation at stimulated locations, whereas activation of the same population early in learning suppressed plateau initiation and place field formation. Together, these findings identify OLM interneurons as the key inhibitory feedback element that dynamically regulates BTSP and stabilizes hippocampal representations during learning.

SUBMITTER: Campbell EP 

PROVIDER: S-EPMC12776205 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature