期刊
NEUROPHARMACOLOGY
卷 208, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2022.108979
关键词
Basal forebrain; Ventral tegmental area; Sleep-wake behavior; Defensive behavior; Glutaminergic neurons
资金
- National Natural Science Foundation of China [81701307, 81601144, 81973083, 81973309, 81701305]
- Innovation of Science and Technology in Fujian Province, China [2016Y9058, 2018Y9089, 2018Y9091]
- Special Support Funds for the Science and Technology Innovation Leader in Fujian Province, China [2016B017]
- Central Financial Support Universities Funds, China [2018L3008]
- Natural Science Foundation of Fujian Province, China [2020J01640, 2021J01685]
- Fujian Provincial Health Technology Projcet [2020QNA037]
- Research Foundation for Advanced Talents at Fujian Medical University, China [XRCZX2017005]
Defensive behavior is essential for animal survival in the natural environment, and a high arousal state and immediate sleep-to-wakefulness transition are required for successful defensive measures. Research has shown that the glutamatergic basal forebrain plays a role in sleep-wake regulation and encodes defensive behaviors through the glutamatergic BF-VTA pathway. Overexcitation of this pathway may be implicated in psychiatric disorders characterized by exaggerated defensive responses.
Defensive behavior, a group of responses that evolved due to threatening stimuli, is crucial for animal survival in the natural environment. For defensive measures to be timely and successful, a high arousal state and immediate sleep-to-wakefulness transition are required. Recently, the glutamatergic basal forebrain (BF) has been implicated in sleep-wake regulation; however, the associated physiological functions and underlying neural circuits remain unknown. Here, using in vivo fiber photometry, we found that BF glutamatergic neuron is activated by various threatening stimuli, including predator odor, looming threat, sound, and tail suspension. Optogenetic activation of BF glutamatergic neurons induced a series of context-dependent defensive behaviors in mice, including escape, fleeing, avoidance, and hiding. Similar to the effects of activated BF glutamatergic cell body, photoactivation of BF glutamatergic terminals in the ventral tegmental area (VTA) strongly drove defensive behaviors in mice. Using synchronous electroencephalogram (EEG)/electromyogram (EMG) recording, we showed that photoactivation of the glutamatergic BF-VTA pathway produced an immediate transition from sleep to wakefulness and significantly increased wakefulness. Collectively, our results clearly demonstrated that the glutamatergic BF is a key neural substrate involved in wakefulness and defensive behaviors, and encodes these behaviors through glutamatergic BF-VTA pathway. Overexcitation of the glutamatergic BF-VTA pathway may be implicated in clinical psychiatric diseases characterized by exaggerated defensive responses, such as autism spectrum disorders.
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