Billeh, Yazan N. and Rodriguez, Alexander V. and Bellesi, Michele and Bernard, Amy and de Vivo, Luisa and Funk, Chadd M. and Harris, Julie and Honjoh, Sakiko and Mihalas, Stefan and Ng, Lydia and Koch, Christof and Cirelli, Chiara and Tononi, Giulio (2016) Effects of Chronic Sleep Restriction during Early Adolescence on the Adult Pattern of Connectivity of Mouse Secondary Motor Cortex. eNeuro, 3 (2). Art. No. 0053-16. ISSN 2373-2822. PMCID PMC4913218. http://resolver.caltech.edu/CaltechAUTHORS:20160706-103941407
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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.
|Additional Information:||Copyright © 2016 Billeh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Received: 9 March 2016; Revised: 14 April 2016; Accepted: 18 April 2016; Published: 22 April 2016. This work was supported by NIMH Grants 1R01MH091326 and R01MH099231 to C.C. and G.T., NINDS Grant P01NS083514 to C.C. and G.T., SciMed GRS Fellowship and NRSA T32 GM007507 to A.R., Wisconsin Distinguished Rath Graduate Fellowship to C.F., and HFSP long-term fellowship LT000263/2012-L to S.H. We thank the Allen Institute founders, P. G. Allen and J. Allen, for their vision, encouragement, and support, and Anh Ho for technical assistance with 2P serial image acquisition. Conflict of Interest: G.T. is involved in a research study in humans supported by Philips Respironics; this study is not related to the work presented in the current paper. The remaining authors have indicated no financial conflicts of interest. Author Contributions: Author contributions: Y.N.B., A.V.R., M.B., L.d.V., C.M.F., S.H., L.N., and C.C. performed research; Y.N.B., A.V.R., M.B., A.B., L.d.V., C.M.F., J.H., S.M., L.N., C.K., C.C., and G.T. analyzed data; A.V.R., M.B., L.d.V., C.M.F., C.C., and G.T. designed research; Y.N.B., A.V.R., M.B., J.H., C.C., and G.T. wrote the paper. Y.N.B. and A.V.R. contributed equally to this work.|
|Group:||Koch Laboratory, KLAB|
|PubMed Central ID:||PMC4913218|
|Official Citation:||Effects of Chronic Sleep Restriction during Early Adolescence on the Adult Pattern of Connectivity of Mouse Secondary Motor Cortex Yazan N. Billeh, Alexander V. Rodriguez, Michele Bellesi, Amy Bernard, Luisa de Vivo, Chadd M. Funk, Julie Harris, Sakiko Honjoh, Stefan Mihalas, Lydia Ng, Christof Koch, Chiara Cirelli, Giulio Tononi eneuro Apr 2016, 3 (2) ENEURO.0053-16.2016; DOI: 10.1523/ENEURO.0053-16.2016|
|Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Tony Diaz|
|Deposited On:||06 Jul 2016 21:08|
|Last Modified:||13 Mar 2017 20:30|
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