Language

English

Publication Date

8-1-2025

Journal

Nature Neuroscience

DOI

10.1038/s41593-025-02004-2

PMID

40721677

PMCID

PMC12321573

PubMedCentral® Posted Date

7-28-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Despite significant progress in characterizing neocortical cell types, a complete understanding of the synaptic connections of individual excitatory cells remains elusive. This study investigates the connectivity of mouse visual cortex thick tufted layer 5 pyramidal cells, also known as extratelencephalic neurons (L5-ETns), using a 1 mm3 publicly available electron microscopy dataset. The analysis reveals that, in their immediate vicinity, L5-ETns primarily establish connections with a group of inhibitory cell types, which, in turn, specifically target the L5-ETns back. The most common excitatory targets of L5-ETns are layer 5 intertelencephalic neurons (L5-ITns) and layer 6 (L6) pyramidal cells, whereas synapses with other L5-ETns are less common. When L5-ETns extend their axons to other cortical regions, they tend to connect more with excitatory cells. Our results highlight a circuit motif where a subclass of excitatory cells forms a subcircuit with specific inhibitory cell types. This is achieved using a publicly available, automated approach for synapse recognition and automated cell typing, offering a framework for exploring the connectivity of other neuron types.

Keywords

Animals, Visual Cortex, Synapses, Mice, Pyramidal Cells, Neurons, Male, Neural circuits, Electron microscopy, Synaptic transmission

Published Open-Access

yes

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