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bioRxiv · 10.1101/2025.06.04.657895

Dendrite-targeting inhibitory interneurons form biased circuits with deep and superficial pyramidal cells in hippocampal CA1

Johantges, A. C.·Hanson, M. A.·Marshall, A. H.·Safa, A.·Payne, E. K.·Bibi, N.·Wester, J. C.
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Abstract

In CA1 hippocampus, pyramidal cells (PCs) can be classified as deep or superficial based on their radial position within the stratum pyramidale. Deep and superficial PCs form biased circuits with perisomatic-targeting PV+ basket cells, but it is unknown if such cell-type-specific circuit motifs extend to dendrite-targeting interneurons. Using male and female mice, we investigated synaptic connectivity and physiology in brain slices from four transgenic lines thought to capture distinct subsets of interneurons: SST-IRES-Cre, Nkx2.1-Cre, Chrna2-Cre, and Htr3a-GFP. First, we found that oriens-lacunosum moleculare (OLM) cells captured by the Chrna2-Cre line are a subset of Htr3a-GFP+ cells in the hippocampus. This novel finding is consistent with previous work showing Nkx2.1-Cre OLM cells are distinct from both Chrna2-Cre and Htr3a-GFP+ cells. Indeed, in paired whole-cell recordings, Nkx2.1-Cre+ interneurons in the stratum oriens, but not Chrna2-Cre+ or Htr3a-GFP+ cells, received more excitatory synaptic connections from superficial PCs relative to deep PCs. Next, we used optogenetic-assisted circuit mapping to investigate inhibition along the proximal and distal dendrites of PCs. We found that superficial PCs received stronger inhibition along their proximal dendrites than deep PCs from SST+ interneurons. Furthermore, this circuit motif was dependent on layer but not PC projection class. Finally, Chrna2-Cre OLM cells provided stronger inhibition to the distal dendrites of deep PCs relative to superficial PCs. Our data reveal that superficial and deep PCs engage in cell-type-specific circuits with dendrite-targeting interneurons. Furthermore, they support that Nkx2.1-Cre OLM cells and Chrna2-Cre/Htr3a-GFP OLM cells are distinct subtypes that form unique circuits in CA1.

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Johantges, A. C., Hanson, M. A., Marshall, A. H., Safa, A., Payne, E. K., Bibi, N., Wester, J. C.. 2025-06-04. Dendrite-targeting inhibitory interneurons form biased circuits with deep and superficial pyramidal cells in hippocampal CA1. https://doi.org/10.1101/2025.06.04.657895

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