Learning-dependent feedback by OLM interneurons shapes CA1 representations

Abstract

Spatial learning depends on hippocampal CA1 place cell representations, which form rapidly through behavioral timescale synaptic plasticity (BTSP). BTSP is driven by dendritic plateau potentials proposed to arise from the interaction of an excitatory target signal from entorhinal cortex layer 3 (EC3) and inhibitory feedback reflecting the current CA1 population state. However, the cellular source of this feedback has remained unknown. Using two-photon Ca2+ imaging in mice during spatial learning, we found that dendrite-targeting oriens-lacunosum moleculare (OLM) interneurons increased their activity at behaviorally salient locations in a manner consistent with previously described environment-specific CA1 representations and EC3 target signals. Causal manipulations revealed that silencing a genetically defined subset of OLM interneurons late in learning enhanced BTSP and place field formation, whereas activating them early suppressed place field formation. These findings identify OLM interneurons as a key inhibitory feedback element regulating BTSP and the formation of hippocampal representations during learning.