Abstract
Throughout childhood and adolescence, periods of heightened neuroplasticity are critical for the development of healthy brain function and behavior. Given the high prevalence of neurodevelopmental disorders, such as autism, identifying disruptors of developmental plasticity represents an essential step for developing strategies for prevention and intervention. Applying a novel computational approach that systematically assessed connections between 436 transcriptional signatures of disease and multiple signatures of neuroplasticity, we identified inflammation as a common pathological process central to a diverse set of diseases predicted to dysregulate plasticity signatures. We tested the hypothesis that inflammation disrupts developmental cortical plasticity in vivo using the mouse ocular dominance model of experience-dependent plasticity in primary visual cortex. We found that the administration of systemic lipopolysaccharide suppressed plasticity during juvenile critical period with accompanying transcriptional changes in a particular set of molecular regulators within primary visual cortex. These findings suggest that inflammation may have unrecognized adverse consequences on the postnatal developmental trajectory and indicate that treating inflammation may reduce the burden of neurodevelopmental disorders.
Footnotes
Authors declare no competing financial interests.
This research was funded by a Traineeship, National Institute of Child Health and Human Development-Interdisciplinary Training in Systems and Developmental Biology and Birth Defects Grant T32H-D0-75735 (to M.R.S.); the Mindich Child Health and Development Institute Pilot Fund (to J.T.D. and H.M.); National Institute of Environmental Health Sciences Grant P30-ES-023515 (to J.T.D. and H.M.), the Knights Templar Eye Foundation (to H.M.); the March of Dimes (to H.M.); the Whitehall Foundation (to H.M.); and National Institutes of Health Grants R01-DK-098242 and U54-CA-189201 (to J.T.D.), R01-EY-024918, R01-EY-026053, and R21 MH106919 (to H.M.).
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