期刊
JOURNAL OF NEUROSCIENCE
卷 41, 期 15, 页码 3462-3478出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2718-20.2021
关键词
arousal; consciousness; DREADDs; gamma; sleep fragmentation; slow oscillations
资金
- NIGMS NIH HHS [R01 GM124248] Funding Source: Medline
Research indicates that activation of preoptic glutamatergic neurons can initiate wakefulness but not maintain arousal from sleep, potentially impacting NREM stability and REM sleep generation.
Clinical and experimental data from the last nine decades indicate that the preoptic area of the hypothalamus is a critical node in a brain network that controls sleep onset and homeostasis. By contrast, we recently reported that a group of glutamatergic neurons in the lateral and medial preoptic area increases wakefulness, challenging the long-standing notion in sleep neurobiology that the preoptic area is exclusively somnogenic. However, the precise role of these subcortical neurons in the control of behavioral state transitions and cortical dynamics remains unknown. Therefore, in this study, we used conditional expression of excitatory hM3Dq receptors in these preoptic glutamatergic (Vglut2(+)) neurons and show that their activation initiates wakefulness, decreases non rapid eye movement (NREM) sleep, and causes a persistent suppression of rapid eye movement (REM) sleep. We also demonstrate, for the first time, that activation of these preoptic glutamatergic neurons causes a high degree of NREM sleep fragmentation, promotes state instability with frequent arousals from sleep, decreases body temperature, and shifts cortical dynamics (including oscillations, connectivity, and complexity) to a more wake-like state. We conclude that a subset of preoptic glutamatergic neurons can initiate, but not maintain, arousals from sleep, and their inactivation may be required for NREM stability and REM sleep generation. Further, these data provide novel empirical evidence supporting the hypothesis that the preoptic area causally contributes to the regulation of both sleep and wakefulness.
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