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Publication : Regulation of wakefulness by astrocytes in the lateral hypothalamus.

First Author  Cai P Year  2022
Journal  Neuropharmacology Volume  221
Pages  109275 PubMed ID  36195131
Mgi Jnum  J:330658 Mgi Id  MGI:7380154
Doi  10.1016/j.neuropharm.2022.109275 Citation  Cai P, et al. (2022) Regulation of wakefulness by astrocytes in the lateral hypothalamus. Neuropharmacology 221:109275
abstractText  The lateral hypothalamus (LH) is an important brain region mediating sleep-wake behavior. Recent evidence has shown that astrocytes in central nervous system modulate the activity of adjacent neurons and participate in several physiological functions. However, the role of LH astrocytes in sleep-wake regulation remains unclear. Here, using synchronous recording of electroencephalogram/electromyogram in mice and calcium signals in LH astrocytes, we show that the activity of LH astrocytes is significantly increased during non-rapid eye movement (NREM) sleep-to-wake transitions and decreased during Wake-to-NREM sleep transitions. Chemogenetic activation of LH astrocytes potently promotes wakefulness and maintains long-term arousal, while chemogenetic inhibition of LH astrocytes decreases the total amount of wakefulness in mice. Moreover, by combining chemogenetics with fiber photometry, we show that activation of LH astrocytes significantly increases the calcium signals of adjacent neurons, especially among GABAergic neurons. Taken together, our results clearly illustrate that LH astrocytes are a key neural substrate regulating wakefulness and encode this behavior through surrounding GABAergic neurons. Our findings raise the possibility that overactivity of LH astrocytes may be an underlying mechanism of clinical sleep disorders.
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