Adaptaciones transcripcionales y fisiológicas de la corteza sensorial primaria después de la pérdida sensorial en el...

Single cell transcriptomics supports cell-specific characterization and the identification of responses to changes in neural activity. Unilateral whisker denervation in adult male and female mice activates post-critical period synaptic plasticity, but the transcriptional responses of neuronal subtypes remain unknown. Single nucleus RNA sequencing and multiplex fluorescence in situ hybridization identified previously unexplored plasticity mechanisms in layer 4 (L4) excitatory neurons in intact sensory cortex. We detected differentially expressed genes related to glutamate receptor signaling and synaptogenesis in thalamocortical (TC) recipient L4 sensory cortex neurons after whisker denervation. L4 excitatory neurons increase expression of glutamate receptors indicative of stabilized and potentiated TC synapses along the intact pathway after unilateral whisker denervation. Immunohistochemistry and electrophysiology determined that intracortical connections to L4 neurons were specifically increased. Transcriptionally unique subtypes of L4 neurons responded uniformly to whisker denervation, highlighting the global upregulation of activity in the intact sensory cortex after unilateral whisker denervation. These adaptations likely underlie the increased cortical activity responding to intact sensory inputs that are observed in rodents and humans after unilateral denervation injury.Significance Statement The adult brain has a remarkable ability to adapt after changes in sensory experience or injury. Here we identified plasticity-related gene programs that were activated in Layer 4 neurons after loss of sensory afferents. These changes occurred in similar ways despite the identified heterogeneity of these cell types. These findings help neuroscientists characterize how the adult brain can adapt after sensory loss.