DSI&DSE Triggered By ECB Participates In Regulating The Effects Of Sleep Deprivation On Learning And Memory In Adolescent Mice

With the rapid development of China's social economy,high-intensity learning&work can be seen everywhere(from school to office building).Under these circumstances,people often sacrifice sleep time in order to complete tasks.Sleep loss has become a relatively common social phenomenon.Adolescents are at an important stage of physical and mental development and often face heavy academic burdens and pressure.Compared to adults,adolescents' bodies need more sleep,but learning tasks make them unable to avoid staying up late or even overnight.Even though the adverse effects of occasional short-term sleep deprivation can be compensated by supplementing sleep,it will still cause irreversible damage to the body if it occurs over years.For some teenagers with strong susceptibility,long-term lack of sleep may lead to a continuous decline in sleep quality,showing a tendency to sleep disorders.Individuals at this stage usually have difficulty falling asleep and have shallow sleep,making it difficult to enter deep sleep.Therefore,the study of the neural mechanism of short-term sleep deprivation impair learning&memory can help with developing regular living and clinical drug intervention of sleep disorder.In this study,the modified multi-platform water environment method was used to deprive animals of REMSD,which mimicked the difficulty of falling asleep and the inability to enter deep sleep.Previous studies have demonstrated that endogenous cannabinoid system(ECS)correlates with sleep and learning&memory respectively,so we started from this system,combined with molecular biology and electrophysiology methods,to explore the impact of ECS in sleep deprivation injury on learning&memory.The male C57BL/6J mice that about 4 weeks year-old were selected for referring to the adolescent period of humans.After 24 hours of REMSD,the anxiety-like behavior of the mice was evaluated using the open field and elevated plus maze;the object-place recognition(OPR)and the Morris water maze(MWM)were used to evaluate learning and memory;the bilateral hippocampus of the mice were stripped and total protein samples were prepared,Western blot was used to determine the protein expression levels of ECS-related synthetase,receptors and degrading enzymes.The electrophysiological data were collected by whole-cell recording mode using brain patch clamp method,and the data was used to analyze the change of ECB-mediated short-term synaptic plasticity(DSE,DSI)after sleep deprivation.The main results are as follows:(1)24-hour REMSD does not affect the anxiety-like behavior of adolescent mice;(2)24-hour REMSD damages the memory extraction of adolescent mice in the OPR task and does not affect the performance in MWM;(3)The expression of MAGL protein in hippocampus of adolescent mice decreased after 24 hours of REMSD,and the expression levels of other proteins did not change significantly;(4)24-hour REMSD impairs the long-term potential of adolescent mice in CA1 area;(5)After 24 hours of REMSD,the amplitude of DSI in hippocampal pyramidal neurons of adolescent mice decreased,and the amplitude of DSE did not change significantly.In summary,24-hour REMSD impairs the performance of adolescent mice at OPR task which requiring more subjective motivational and showing low motivation levels.But it does not affect performance in MWM which does not requiring more subjective motivational and showing high motivation levels.These phenomena may be related to the level of ECS activity in hippocampus.ECS can reduce the damage of REMSD by down regulating the MAGL level.However,for low-motility tasks,a lower level of MAGL may be required to effectively alleviate.Lower levels of MAGL mean higher 2-AG concentrations in the synaptic cleft,and more tonic activation of the inhibitory postsynaptic CB1R(can effectively increase the excitability of regional neurons).