Molecular states underlying neuronal cell type development and plasticity in the whisker cortex

Abstract

Mouse whisker somatosensory cortex (wS1) is a major model system to study the experience-dependent plasticity of cortical neuron physiology, morphology, and sensory coding. However, the role of sensory experience in regulating neuronal cell type development and gene expression in wS1 remains poorly understood. We assembled and annotated a transcriptomic atlas of wS1 during postnatal development comprising 45 molecularly distinct neuronal types that can be grouped into eight excitatory and four inhibitory neuron subclasses. Using this atlas, we examined the influence of whisker experience from postnatal day (P) 12, the onset of active whisking, to P22, on the maturation of molecularly distinct cell types. During this developmental period, when whisker experience was normal, [~]250 genes were regulated in a neuronal subclass-specific fashion. At the resolution of neuronal types, we found that only the composition of layer (L) 2/3 glutamatergic neuronal types, but not other neuronal types, changed substantially between P12 and P22. These compositional changes resemble those observed previously in the primary visual cortex (V1), and the temporal gene expression changes were also highly conserved between the two regions. In contrast to V1, however, cell type maturation in wS1 is not substantially dependent on sensory experience, as 10-day full-face whisker deprivation did not influence the transcriptomic identity and composition of L2/3 neuronal types. A one-day competitive whisker deprivation protocol also did not affect cell type identity but induced moderate changes in plasticity-related gene expression. Thus, developmental maturation of cell types is similar in V1 and wS1, but sensory deprivation minimally affects cell type development in wS1. Highlights- A single-nucleus transcriptomic atlas of the whisker somatosensory cortex (wS1) during early postnatal development - Different neuronal subclasses in wS1 show distinct developmental gene expression changes - The composition of L2/3 glutamatergic neurons changes between the second and the third postnatal week - Developmental gene expression and cell type changes are conserved between wS1 and the primary visual cortex (V1) - Unlike V1, these changes are not affected by prolonged sensory deprivation - Brief whisker deprivation induces subclass-specific activity-dependent gene expression in a whisker column-specific fashion