The Synaptic Architecture of Layer 5 Thick Tufted Excitatory Neurons in the Visual Cortex of Mice
Author:
Bodor Agnes L.ORCID, Schneider-Mizell Casey MORCID, Zhang ChiORCID, Elabbady LeilaORCID, Mallen Alex, Bergeson Andi, Brittain DerrickORCID, Buchanan JoAnnORCID, Bumbarger Daniel J., Dalley RachelORCID, Gamlin ClareORCID, Joyce EmilyORCID, Kapner Daniel, Kinn SamORCID, Mahalingam GayathriORCID, Seshamani SharmishtaaORCID, Suckow Shelby, Takeno MarcORCID, Torres RusselORCID, Yin WenjingORCID, Bae J. AlexanderORCID, Castro Manuel A., Dorkenwald SvenORCID, Halageri AkhileshORCID, Jia Zhen, Jordan Chris, Kemnitz NicoORCID, Lee KisukORCID, Li Kai, Lu RanORCID, Macrina ThomasORCID, Mitchell Eric, Mondal Shanka Subhra, Mu Shang, Nehoran BarakORCID, Popovych Sergiy, Silversmith WilliamORCID, Turner Nicholas L.ORCID, Yu Szi-chiehORCID, Wong William, Wu JingpengORCID, Celii Brendan, Campagnola Luke, Seeman Stephanie C, Jarsky Tim, Ren Naixin, Arkhipov Anton, Reimer Jacob, Seung H SebastianORCID, Reid R. ClayORCID, Collman ForrestORCID, Maçarico da Costa NunoORCID,
Abstract
SummaryThe neocortex is one of the most critical structures that makes us human, and it is involved in a variety of cognitive functions from perception to sensory integration and motor control. Composed of repeated modules, or microcircuits, the neocortex relies on distinct cell types as its fundamental building blocks. Despite significant progress in characterizing these cell types1–5, an understanding of the complete synaptic partners associated with individual excitatory cell types remain elusive.Here, we investigate the connectivity of arguably the most well recognized and studied excitatory neuron in the neocortex: the thick tufted layer 5 pyramidal cell6–10also known as extra telencephalic (ET)11neurons. Although the synaptic interactions of ET neurons have been extensively explored, a comprehensive characterization of their local connectivity remains lacking. To address this knowledge gap, we leveraged a 1 mm3electron microscopic (EM) dataset.We found that ET neurons primarily establish connections with inhibitory cells in their immediate vicinity. However, when they extend their axons to other cortical regions, they tend to connect more with excitatory cells. We also find that the inhibitory cells targeted by ET neurons are a specific group of cell types, and they preferentially inhibit ET cells. Finally, we observed that the most common excitatory targets of ET neurons are layer 5 IT neurons and layer 6 pyramidal cells, whereas synapses with other ET neurons are not as common.These findings challenge current views of the connectivity of ET neurons and suggest a circuit design that involves local competition among ET neurons and collaboration with other types of excitatory cells. Our results also highlight a specific circuit pattern where a subclass of excitatory cells forms a network with specific inhibitory cell types, offering a framework for exploring the connectivity of other types of excitatory cells.
Publisher
Cold Spring Harbor Laboratory
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