Neocortical layer 4 in adult mouse differs in major cell types and circuit organization between primary 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 almost all Somatostatin-positive (SOM+) neurons were Martinotti cells. In contrast, in somatosensory cortex (S1), excitatory cells were mostly stellate and SOM+ cells were non-Martinotti. These morphologically distinct SOM+ interneurons correspond to different transcriptomic cell types and are differentially integrated into the local circuit with only S1 cells receiving local excitatory input. Our results challenge the classical view of a canonical microcircuit repeated through the neocortex. Instead we propose that cell-type specific circuit motifs, such as the Martinotti/pyramidal pair, are optionally used across the cortex as building blocks to assemble cortical circuits.