A chemical-genetic investigation of BDNF-NtrkB signaling in mammalian sleep

[摘要] Study Objectives The neurotrophin brain-derived neurotrophic factor (BDNF) is hypothesized to be a molecular mediator of mammalian sleep homeostasis. This hypothesis is supported by correlational findings and results obtained from pharmacology. BDNF binds with high affinity to the membrane-bound receptor Neurotrophin Tyrosine Kinase Receptor B (NtrkB), which triggers several intracellular signaling cascades. It is therefore possible that BDNF’s role in sleep homeostasis is mediated via NtrkB. We examined this hypothesis using a chemical-genetic technique that allows for rapid and selective inhibition of NtrkB in vivo.Methods We used mutant mice bearing a point mutation in the NtrkB that allows for selective and reversible inactivation in the presence of a small binding molecule (1-NM-PP1). Using a crossover design, we determined the effects of NtrkB inhibition on baseline sleep architecture and sleep homeostasis.Results We find that NtrkB inhibition reduced rapid eye movement (REM) sleep time and changed state transitions but had no effect on sleep homeostasis.Conclusions These findings suggest that BDNF-NtrkB receptor signaling has subtle roles in sleep architecture, but no role in sleep homeostasis.

[学科分类] 生理学

[关键词] neurotrophin;REM;homeostasis;plasticity;scaling