title: Effects of Chronic Sleep Restriction during Early Adolescence on the Adult Pattern of Connectivity of Mouse Secondary Motor Cortex.
abstract: 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.
authors.affiliation: Computation and Neural Systems Program, California Institute of Technology , Pasadena, California 91125.
authors.forename: Yazan N
authors.initials: YN
authors.lastname: Billeh
authors.affiliation: Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin 53719; Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53705.
authors.forename: Alexander V
authors.identifier: 0000-0002-0547-8842
authors.initials: AV
authors.lastname: Rodriguez
authors.affiliation: Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin 53719; Department of Experimental and Clinical Medicine, Section of Neuroscience and Cell Biology, Università Politecnica delle Marche, Torrette di Ancona, Ancona, Italy 60020.
authors.forename: Michele
authors.identifier: 0000-0002-3922-0188
authors.initials: M
authors.lastname: Bellesi
authors.affiliation: Allen Institute for Brain Science , Seattle, Washington 98109.
authors.forename: Amy
authors.initials: A
authors.lastname: Bernard
authors.affiliation: Department of Psychiatry, University of Wisconsin-Madison , Madison, Wisconsin 53719.
authors.forename: Luisa
authors.initials: L
authors.lastname: de Vivo
authors.affiliation: Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin 53719; Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin 53705; Medical Scientist Training Program, University of Wisconsin-Madison, Health Sciences Learning Center, Madison, Wisconsin 53705.
authors.forename: Chadd M
authors.identifier: 0000-0001-6399-7803
authors.initials: CM
authors.lastname: Funk
authors.affiliation: Allen Institute for Brain Science , Seattle, Washington 98109.
authors.forename: Julie
authors.identifier: 0000-0003-0820-2021
authors.initials: J
authors.lastname: Harris
authors.affiliation: Department of Psychiatry, University of Wisconsin-Madison , Madison, Wisconsin 53719.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Honjoh
authors.affiliation: Allen Institute for Brain Science , Seattle, Washington 98109.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mihalas
authors.affiliation: Allen Institute for Brain Science , Seattle, Washington 98109.
authors.forename: Lydia
authors.initials: L
authors.lastname: Ng
authors.affiliation: Allen Institute for Brain Science , Seattle, Washington 98109.
authors.forename: Christof
authors.initials: C
authors.lastname: Koch
authors.affiliation: Department of Psychiatry, University of Wisconsin-Madison , Madison, Wisconsin 53719.
authors.forename: Chiara
authors.identifier: 0000-0003-2563-677X
authors.initials: C
authors.lastname: Cirelli
authors.affiliation: Department of Psychiatry, University of Wisconsin-Madison , Madison, Wisconsin 53719.
authors.forename: Giulio
authors.initials: G
authors.lastname: Tononi
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D004569:Electroencephalography; D007839:Functional Laterality; D006801:Humans; D016014:Linear Models; D000069550:Machine Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D009044:Motor Cortex / Q000503:physiopathology*; D009415:Nerve Net / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D012892:Sleep Deprivation / Q000473:pathology* / Q000503:physiopathology; D014161:Transduction, Genetic
chemical_list: D002352:Carrier Proteins; C477609:Elg1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins
keywords: adolescence; secondary motor cortex; sensitive period; sleep loss