Khalid, R.; Masini, D.; Locarno, A.; Netsyk, O.; Lorentz, J.; Broberger, C.

Persistent subplate neurons in layer 6b (L6b) of the cerebral cortex have long been assumed to be a passive remnant of early development. Recent findings are challenging this concept, but the functional role of L6b remains mysterious. A large group of L6b neurons express Connective Tissue Growth Factor (Ctgf). Here, we mapped L6b-Ctgf neurons throughout the cortex and found the highest density in primary sensorimotor areas. Cortical L6b-Ctgf projections are ipsilaterally restricted and origin-site specific, with notable reciprocity, whereas innervation of the thalamus is modality-matched. L6b-Ctgf neurons are electrically diverse and form excitatory synapses with both pyramidal cells and interneurons. In freely moving mice, these neurons are highly active and have prominent task-specific and temporally locked responses to external stimuli. These responses are dominated by paradoxical population silencing with escalating task engagement. Thus, L6b-Ctgf neurons may keep cortical ensembles in a state of alertness and available to process cognate stimuli.