Cell type composition and circuit organization of clonally related excitatory neurons in the juvenile mouse neocortex.

Clones of excitatory neurons derived from a common progenitor have been proposed to serve as elementary information processing modules in the neocortex. To characterize the cell types and circuit diagram of clonally related excitatory neurons, we performed multi-cell patch clamp recordings and Patch-seq on neurons derived from Nestin-positive progenitors labeled by tamoxifen induction at embryonic day 10.5. The resulting clones are derived from two radial glia on average, span cortical layers 2-6, and are composed of a random sampling of transcriptomic cell types. We find an interaction between shared lineage and connection type: related neurons are more likely to be connected vertically across cortical layers, but not laterally within the same layer. These findings challenge the view that related neurons show uniformly increased connectivity and suggest that integration of vertical intra-clonal input with lateral inter-clonal input may represent a developmentally programmed connectivity motif supporting the emergence of functional circuits.

Layer 4 of mouse neocortex differs in cell types and circuit organization between sensory areas.

Layer 4 (L4) of mammalian neocortex plays a crucial role in cortical information processing, yet a complete census of its cell types and connectivity remains elusive. Using whole-cell recordings with morphological recovery, we identified one major excitatory and seven inhibitory types of neurons in L4 of adult mouse visual cortex (V1). Nearly all excitatory neurons were pyramidal and all somatostatin-positive (SOM+) non-fast-spiking interneurons were Martinotti cells. In contrast, in somatosensory cortex (S1), excitatory neurons were mostly stellate and SOM+ interneurons were non-Martinotti. These morphologically distinct SOM+ interneurons corresponded to different transcriptomic cell types and were differentially integrated into the local circuit with only S1 neurons receiving local excitatory input. We propose that cell type specific circuit motifs, such as the Martinotti/pyramidal and non-Martinotti/stellate pairs, are used across the cortex as building blocks to assemble cortical circuits.

Author Correction: Layer 4 of mouse neocortex differs in cell types and circuit organization between sensory areas.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.