Cortex-Wide Neuron Activation after Traumatic Brain Injury in Mice.

Following a traumatic brain injury (TBI), the neocortex undergoes time-dependent cellular responses including immediate tissue deformation, enhanced excitability, and elevated expression of immediate early genes. However, the spatial extent of early neuronal activity after a focal injury remains unclear. Here we use targeted recombination in active populations reporter mice of both sexes to identify neurons activated in the acute phase following a controlled cortical impact injury applied to the somatosensory neocortex. We find widespread cell activation across large portions of the cortex that extends beyond the astrocytic and microglial responses marking the injury site. Activated cells are predominantly neurons, and few cells colabel with GFAP or IBA1. Our findings reveal that even focal injury engages cortical circuits across large portions of the injured brain, highlighting the importance of considering cortex-wide neuronal dynamics in the early postinjury period and their potential impact on network excitability, remodeling, and recovery.