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Semaphorin 3A promotes resilience of sleep and cognition to brain injury

Necula, D.; Voskobiynyk, Y.; Poluri, S.; Paz, J. T.

2026-06-30 neuroscience
10.64898/2026.06.24.734382 bioRxiv
Show abstract

Chronic sleep disruption and cognitive deficits are debilitating long-term consequences of traumatic brain injury (TBI), yet the endogenous mechanisms that drive network-level recovery remain poorly understood. Here, we demonstrate that during the chronic phase post-injury, network oscillations critical for memory, including slow oscillations, delta waves, and sleep spindles, undergo precise adaptive tuning that sustains sleep-dependent memory consolidation. This functional circuit resilience requires Semaphorin-3A (Sema3a); loss of Sema3a function prevents the protective reorganization of non-rapid eye movement (NREM) sleep architecture, impairs sleep-dependent memory consolidation, and exacerbates cortical lesion size. Together, these findings identify Sema3a as an innate protective mechanism that preserves sleep architecture and cognitive function following TBI.

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