Endocannabinoid-mediated rescue of somatosensory cortex activity, plasticity and related behaviors following an early-life concussion in male mice

Due to the assumed plasticity of the immature brain, early-life brain alterations are thought to lead to better recoveries in comparison to the mature brain. Despite clinical needs, how neuronal networks and associated behaviors are affected by early-life brain stresses, such as pediatric concussions, have been overlooked. Here we provide first evidence in male mice that a single early-life concussion durably increases neuronal activity in the somatosensory cortex into adulthood, disrupting neuronal integration while the animal is performing sensory-related tasks.

This represents a clinically relevant mechanism that was previously unappreciated for understanding impairment of sensory-related behavior performance. We also demonstrate that pharmacological modulation of the endocannabinoid system a year post-concussion is well-suited to rescue neuronal activity and plasticity, and normalizes sensory-related behavioral performance. These findings identify persistent alterations in cortical sensory processing following early-life concussion and demonstrate that neuronal and behavioral deficits remain amenable to pharmacological intervention long after injury.

We thank Richard Rouland and Jonathan Zapata for experimental advice and helpful discussions. This research project was funded by Eranet Neuron MISST and Neuvasc (JB), Agence Nationale de la recherche (JB), Nanospace (JB) and NIH, Grant No. (1R01NS119605-01 AO and JB). La Rochelle, CEBC, UMR7372, F-79360, Villiers-en-bois, France Univ.

Bordeaux, CNRS, CRMSB, UMR-5536, F-33000, Bordeaux, France Jérôme BADAUT, Lea HIPPAUF, Mathilde MALINCONI & Christophe J. DUBOIS Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA Department of Pediatrics, University of California, Irvine, CA, USA Division of Biomedical Sciences, School of Medicine, University of California, Riverside, CA, USA The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. BADAUT, J., HIPPAUF, L., MALINCONI, M. et al. Endocannabinoid-mediated rescue of somatosensory cortex activity, plasticity and related behaviors following an early-life concussion in male mice.