Orexin neurons within the lateral hypothalamus play a crucial role in the promotion and maintenance of arousal. Studies have strongly suggested that orexin neurons are an important target in endogenous adenosine-regul...Orexin neurons within the lateral hypothalamus play a crucial role in the promotion and maintenance of arousal. Studies have strongly suggested that orexin neurons are an important target in endogenous adenosine-regulated sleep homeostasis. Orexin A induces a robust increase in the firing activity of orexin neurons, while adenosine has an inhibitory effect. Whether the excitatory action of orexins in the lateral hypothalamus actually promotes wakefulness and reverses the sleep-producing effect of adenosine in vivo is less clear. In this study, electroencephalographic and electromyographic recordings were used to investigate the effects of orexin A and adenosine on sleep and wakefulness in rats. We found that microinjection of orexin A into the lateral hypothalamus increased wakefulness with a concomitant reduction of sleep during the first 3 h of post-injection recording, and this was completely blocked by a selective antagonist for orexin receptor 1, SB 334867. The enhancement of wakefulness also occurred after application of the excitatory neurotransmitter glutamate in the first 3 h post-injection. However, in the presence of the NMDA receptor antagonist APV, orexin A did not induce any change of sleep and wakefulness in the first 3 h. Further, exogenous application of adenosine into the lateral hypothalamus induced a marked increase of sleep in the first 3-h post-injection. No significant change in sleep and wakefulness was detected after adenosine application followed by orexin A administration into the same brain area. Thesefindings suggest that the sleep-promoting action of adenosine can be reversed by orexin A applied to the lateral hypothalamus, perhaps by exciting glutamatergic input to orexin neurons via the action of orexin receptor 1.展开更多
Alzheimer's disease(AD)is a progressive neurodegenerative disorder associated with cognitive impairment in older adults.The accumulation of insoluble forms of amyloid-β(Aβ)in plaques in extracellular spaces and ...Alzheimer's disease(AD)is a progressive neurodegenerative disorder associated with cognitive impairment in older adults.The accumulation of insoluble forms of amyloid-β(Aβ)in plaques in extracellular spaces and the aggregation of hyperphosphorylated microtubule-associated protein tau in neurofibrillary tangles in neurons are considered to be central pathological features of A D[1,2].展开更多
Optogenetics is a newly-introduced technology in the life sciences and is gaining increasing attention.It refers to the combination of optical technologies and genetic methods to control the activity of specific cell ...Optogenetics is a newly-introduced technology in the life sciences and is gaining increasing attention.It refers to the combination of optical technologies and genetic methods to control the activity of specific cell groups in living tissue,during which high-resolution spatial and temporal manipulation of cells is achieved.Optogenetics has been applied to numerous regions,including cerebral cortex,hippocampus,ventral tegmental area,nucleus accumbens,striatum,spinal cord,and retina,and has revealed new directions of research in neuroscience and the treatment of related diseases.Since optogenetic tools are controllable at high spatial and temporal resolution,we discuss its applications in these regions in detail and the recent understanding of higher brain functions,such as reward-seeking,learning and memory,and sleep.Further,the possibilities of improved utility of this newly-emerging technology are discussed.We intend to provide a paradigm of the latest advances in neuroscience using optogenetics.展开更多
Sleep is a universal biological process occurring in almost every species of animal,and the loss of sleep has detrimental effects,especially impairments in cognition[1,2].Yet,the neuronal function of sleep is still on...Sleep is a universal biological process occurring in almost every species of animal,and the loss of sleep has detrimental effects,especially impairments in cognition[1,2].Yet,the neuronal function of sleep is still one of the greatest mysteries.One prominent idea,known as the synaptic homeostasis hypothesis,展开更多
基金supported by the National Natural Science Foundation of China(81071074)
文摘Orexin neurons within the lateral hypothalamus play a crucial role in the promotion and maintenance of arousal. Studies have strongly suggested that orexin neurons are an important target in endogenous adenosine-regulated sleep homeostasis. Orexin A induces a robust increase in the firing activity of orexin neurons, while adenosine has an inhibitory effect. Whether the excitatory action of orexins in the lateral hypothalamus actually promotes wakefulness and reverses the sleep-producing effect of adenosine in vivo is less clear. In this study, electroencephalographic and electromyographic recordings were used to investigate the effects of orexin A and adenosine on sleep and wakefulness in rats. We found that microinjection of orexin A into the lateral hypothalamus increased wakefulness with a concomitant reduction of sleep during the first 3 h of post-injection recording, and this was completely blocked by a selective antagonist for orexin receptor 1, SB 334867. The enhancement of wakefulness also occurred after application of the excitatory neurotransmitter glutamate in the first 3 h post-injection. However, in the presence of the NMDA receptor antagonist APV, orexin A did not induce any change of sleep and wakefulness in the first 3 h. Further, exogenous application of adenosine into the lateral hypothalamus induced a marked increase of sleep in the first 3-h post-injection. No significant change in sleep and wakefulness was detected after adenosine application followed by orexin A administration into the same brain area. Thesefindings suggest that the sleep-promoting action of adenosine can be reversed by orexin A applied to the lateral hypothalamus, perhaps by exciting glutamatergic input to orexin neurons via the action of orexin receptor 1.
文摘Alzheimer's disease(AD)is a progressive neurodegenerative disorder associated with cognitive impairment in older adults.The accumulation of insoluble forms of amyloid-β(Aβ)in plaques in extracellular spaces and the aggregation of hyperphosphorylated microtubule-associated protein tau in neurofibrillary tangles in neurons are considered to be central pathological features of A D[1,2].
基金supported by the National Basic Research Program of China (2011CB503700)
文摘Optogenetics is a newly-introduced technology in the life sciences and is gaining increasing attention.It refers to the combination of optical technologies and genetic methods to control the activity of specific cell groups in living tissue,during which high-resolution spatial and temporal manipulation of cells is achieved.Optogenetics has been applied to numerous regions,including cerebral cortex,hippocampus,ventral tegmental area,nucleus accumbens,striatum,spinal cord,and retina,and has revealed new directions of research in neuroscience and the treatment of related diseases.Since optogenetic tools are controllable at high spatial and temporal resolution,we discuss its applications in these regions in detail and the recent understanding of higher brain functions,such as reward-seeking,learning and memory,and sleep.Further,the possibilities of improved utility of this newly-emerging technology are discussed.We intend to provide a paradigm of the latest advances in neuroscience using optogenetics.
文摘Sleep is a universal biological process occurring in almost every species of animal,and the loss of sleep has detrimental effects,especially impairments in cognition[1,2].Yet,the neuronal function of sleep is still one of the greatest mysteries.One prominent idea,known as the synaptic homeostasis hypothesis,