| 要旨 |
Sleep–wake cycles are regulated by the alternate activation of sleep- and wake-promoting neurons. However, recent evidence indicates important roles of glial cells in various brain functions and behaviours. Astrocytes, for example, play important roles in regulating synaptic transmission and plasticity, including fine-tuning of glutamate transmission through glutamate transporter-1 (GLT1). We have been investigating the role of astrocytes in regulating glutamatergic and GABAergic transmission to wake-promoting orexin (ORX) and sleep-promoting melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus. Brief (6 hours) sleep deprivation bidirectionally altered the perisomatic coverage wit GLT1 in ORX and MCH neurons. In ORX neurons, a decrease in GLT1 apposition paralleled tonic presynaptic inhibition through activation of Group III mGluRs, which would promote sleep transition after sleep loss. These changes were reversed following 3 hours of ad lib sleep. One possible explanation for the GLT1 plasticity is the structural remodeling of perisynaptic astrocytic processes. To investigate this possibility, we have been using correlative light-electron microscopy with serial 3D reconstruction. Astrocytes are present at the majority of synapses to ORX neurons, at 200-400 nm from the synaptic cleft. The effect of sleep history on this distance is currently under investigation. Interestingly, a large part (~70%) of the cell bodies as well as dendrites of ORX neurons is wrapped with very thin (~100 nm) astrocytic sheets. When axon terminals approach ORX neurons, astrocytic processes move away to allow synapse formation. Collectively, these findings to date indicate that astrocytes may play an important role in regulating the activity of sleep/wake-regulatory neurons homeostatically according to the level of sleep need.
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