RT Journal Article SR Electronic T1 Effects of Chronic Sleep Restriction during Early Adolescence on the Adult Pattern of Connectivity of Mouse Secondary Motor Cortex JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0053-16.2016 DO 10.1523/ENEURO.0053-16.2016 VO 3 IS 2 A1 Billeh, Yazan N. A1 Rodriguez, Alexander V. A1 Bellesi, Michele A1 Bernard, Amy A1 de Vivo, Luisa A1 Funk, Chadd M. A1 Harris, Julie A1 Honjoh, Sakiko A1 Mihalas, Stefan A1 Ng, Lydia A1 Koch, Christof A1 Cirelli, Chiara A1 Tononi, Giulio YR 2016 UL http://www.eneuro.org/content/3/2/ENEURO.0053-16.2016.abstract AB Cortical circuits mature in stages, from early synaptogenesis and synaptic pruning to late synaptic refinement, resulting in the adult anatomical connection matrix. Because the mature matrix is largely fixed, genetic or environmental factors interfering with its establishment can have irreversible effects. Sleep disruption is rarely considered among those factors, and previous studies have focused on very young animals and the acute effects of sleep deprivation on neuronal morphology and cortical plasticity. Adolescence is a sensitive time for brain remodeling, yet whether chronic sleep restriction (CSR) during adolescence has long-term effects on brain connectivity remains unclear. We used viral-mediated axonal labeling and serial two-photon tomography to measure brain-wide projections from secondary motor cortex (MOs), a high-order area with diffuse projections. For each MOs target, we calculated the projection fraction, a combined measure of passing fibers and axonal terminals normalized for the size of each target. We found no homogeneous differences in MOs projection fraction between mice subjected to 5 days of CSR during early adolescence (P25–P30, ≥50% decrease in daily sleep, n=14) and siblings that slept undisturbed (n=14). Machine learning algorithms, however, classified animals at significantly above chance levels, indicating that differences between the two groups exist, but are subtle and heterogeneous. Thus, sleep disruption in early adolescence may affect adult brain connectivity. However, because our method relies on a global measure of projection density and was not previously used to measure connectivity changes due to behavioral manipulations, definitive conclusions on the long-term structural effects of early CSR require additional experiments.