Khalid, R. | Search bioRxiv

bioRxiv2026

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

neuroscience↗

bioRxiv2025

Monoaminergic neurons share transcriptional identity across Bilaterian animals

The evolutionary conservation of cell types over deep time has long been theorised but remains difficult to demonstrate. Monoaminergic neurons, which produce molecules such as serotonin and dopamine, are central to animal behaviour and cognition, yet their evolutionary origins remain unresolved. Here, we analysed single-cell transcriptomes from 16 metazoan species spanning eight phyla. Using a novel integration method, Orthogroup Recoding, together with experimental validation, we show that monoaminergic neurons form consistent transcriptional clusters across Bilateria. These clusters share a regulatory signature involving conserved transcription factors, including homologues of Fev, Lmx1b, Fer2, Insm, and Isl, suggesting a common regulatory program. This signature extends beyond the brain including other monoaminergic cells, such as the gut enterochromaffin cells and larval sensory neurons. By contrast, non-bilaterian lineages lack the coordinated expression of the transcription factors and the biosynthetic machinery that regulate monoamine production. Our observations support the existence of a shared set of TFs that define monoaminergic identity across in bilaterians.

bioinformatics↗