Cortical Layer 6b Persistent Subplate Neurons Reciprocally Connect Sensorimotor Areas and Inversely Reflect Somatosensory Engagement

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 L6bCtgf neurons throughout the cortex and found the highest density in primary sensorimotor areas. Cortical L6bCtgf projections are ipsilaterally restricted and origin-site specific, with notable reciprocity, whereas innervation of the thalamus is modality-matched. L6bCtgf 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, L6bCtgf neurons may keep cortical ensembles in a state of alertness and available to process cognate stimuli. HIGHLIGHTSO_LIL6bCtgf neurons form origin-and layer-specific ipsilateral cortical connections. C_LIO_LIElectrically heterogeneous L6bCtgf neurons excite multiple classes of cortical neurons. C_LIO_LIBarrel cortex L6bCtgf neurons are highly active in freely moving mice. C_LIO_LISomatosensory exploration paradoxically silences active barrel cortex L6bCtgf neurons. C_LI