Mild traumatic brain injury (mTBI) is a prevalent health concern, with more than 2.5 million cases occurring annually in the United States. Acute signs and symptoms of mTBIs may involve physical symptoms, as well as emotional, cognitive, and sleep-related issues. The underlying mechanisms of these symptoms remain elusive. Here, we describe that repeated closed skull mTBIs in mice are associated with acute behavioral deficits. We found that optogenetic-induced spreading depolarizations (SDs) are associated with similar behavioral deficits. Using in vivo electrophysiology, we confirmed the depression of cortical network activity following optogenetic-induced SDs. The timing of the high-frequency activity recovery coincided with the recovery of voluntary movement. Following the depression, there was a prolonged period of increased power in low frequencies (<30 Hz). Cortical dysfunction coincided temporally with motor behavioral deficits in the neurological severity score tasks. Our study provides evidence that repeated mTBIs or SDs are associated with worse behavioral deficits.
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