Transient synaptic refinement and glial adaptations after whisker denervation in adult mice

Loss of sensation after injury causes profound changes in neural circuits, impacting sensory perception and recovery. Overcoming sensory loss requires neural plasticity to support accurate processing of remaining sensory afferents, but the mechanisms by which circuit plasticity occurs in adults are not well understood. Despite decades of studies manipulating the mouse whisker sensory system, the impact of sex, glial activity, and time since injury has not yet been clarified. We performed unilateral whisker denervation in adult male and female mice and characterized synaptic and glial responses at multiple time points after injury. We determined that whisker denervation leads to a transient loss of thalamocortical and intracortical putative excitatory synapses in the deprived sensory cortex. This loss corresponds with a transient shift in microglial morphology, with increased proportions of ramified-shaped microglia and decreased proportions of amoeboid-shaped microglia. Most of these results were more robust in female mice, highlighting the importance of powering studies for sex-specific adaptations. Importantly, these results identify temporally restricted circuit plasticity that should be considered when implementing post-injury interventions to support recovery.