The Synaptic Architecture of Layer 5 Thick Tufted Excitatory Neurons in the Visual Cortex of Mice

The neocortex is composed of microcircuits built from distinct cell types. Despite significant progress in characterizing these cell types, understanding the full synaptic connections of individual excitatory cells remains elusive. This study investigates the connectivity of arguably the most well recognized excitatory neuron in the neocortex: the thick tufted layer 5 pyramidal cell also known as extra telencephalic (ET) neurons using a 1 mm3 publicly available electron microscopy dataset. The analysis reveals that in their immediate vicinity ET neurons primarily establish recurrent connections with a specific group of inhibitory cell types. 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. When ET cells extend their axons to other cortical regions, they tend to connect more with excitatory cells. Our results highlight a specific circuit pattern of a L5ET neuron using an automated approach for synapse recognition and automated cell typing, which is publicly available offering a framework for exploring the connectivity of other neuron types.