@article {NagaiENEURO.0077-21.2021, author = {Hirotaka Nagai and Luisa de Vivo and William Marshall and Giulio Tononi and Chiara Cirelli}, title = {Effects of Severe Sleep Disruption on the Synaptic Ultrastructure of Young Mice}, volume = {8}, number = {4}, elocation-id = {ENEURO.0077-21.2021}, year = {2021}, doi = {10.1523/ENEURO.0077-21.2021}, publisher = {Society for Neuroscience}, abstract = {There is molecular, electrophysiological, and ultrastructural evidence that a net increase in synaptic strength occurs in many brain circuits during spontaneous wake (SW) or short sleep deprivation, reflecting ongoing learning. Sleep leads instead to a broad but selective weakening of many forebrain synapses, thus preventing synaptic saturation and decreasing the energy cost of synaptic activity. Whether synaptic potentiation can persist or further increase after long sleep deprivation is unknown. Whether synaptic renormalization can occur during chronic sleep restriction (CSR) is also unknown. Here, we addressed these questions by measuring an established ultrastructural measure of synaptic strength, the axon-spine interface (ASI), in the primary motor cortex (M1) of (1) one-month-old adolescent mice CSR using a paradigm that decreases NREM and REM sleep by two/thirds; (2) in two-week-old mouse pups sleep deprived for 15 h, or allowed afterward to recover for 16 h. Both groups were compared with mice of the same age that were asleep or awake for a few hours (both sexes). The ASI size of CSR mice (n = 3) was comparable to that measured after SW or short sleep deprivation and larger than after sleep (n = 4/group). In pups, the ASI size increased after short sleep loss (n = 3) relative to sleep (n = 4), fell below sleep levels after long sleep deprivation (n = 4), and remained low after recovery (n = 3). Long sleep deprived pups also lost some weight. These results suggest that (1) severe sleep restriction is incompatible with synaptic renormalization; (2) very young mice cannot maintain high synaptic strength during prolonged wake.}, URL = {https://www.eneuro.org/content/8/4/ENEURO.0077-21.2021}, eprint = {https://www.eneuro.org/content/8/4/ENEURO.0077-21.2021.full.pdf}, journal = {eNeuro} }