Summary: Researchers have identified neurons that appear to play a critical role in connecting sleep and emotions. The findings provide an important insight into the pathophysiology of insomnia and the role of orexin in arousal regulation. Researchers hope their findings will lead to new remedies for sleep disorders.
Source: University of Tsukuba.
You may have experienced sleepless nights when you were anxious, stressed or too excited. Such emotions are well-known to affect wakefulness and can even cause insomnia, though the underlying mechanisms in our brain have still been unclear. Scientists in the Sleep Institute in Japan spotted neurons that play crucial roles in connecting emotions and sleep, shedding light on the future discovery of drug targets for anxiety disorder and/or sleep disorders.
Encountering predators, adapting to a novel environment or expecting a reward ? these stressful or emotionally-salient situations require animals to shift their behavior to a vigilant state, altering their physiological conditions through modulation of autonomic and endocrine functions.
The bed nucleus of the stria terminalis (BNST) is a part of the extended amygdala, which is generally considered as a key player in stress response, fear and anxiety. Through projections to various brain regions including relay nuclei of the autonomic nervous system, hypothalamic regions and the central nucleus of the amygdala, the BNST controls endocrine and autonomic reactions in response to emotionally-salient stimuli, along with behavioral expression of anxiety and fear.
A group of researchers led by Takeshi Sakurai, Vice Director of the International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, found that acute optogenetic excitation of GABAergic neurons in BNST during non-rapid eye movement (NREM) sleep in mice resulted in immediate transition to a wakefulness state without the function of orexins, highly important neuropeptides for maintaining wakefulness. Notably, stimulation of the same neurons during REM sleep did not show any effects on sleep/wakefulness states.
Prolonged excitation of GABAergic neurons in BNST by a chemogenetic method evoked a longer-lasting, sustained wakefulness state, and it was abolished by administering a dual orexin receptor blocker (antagonist) DORA 22 in advance, meaning that orexins are involved in this phenomenon.
“Our study revealed a role of the BNST GABAergic system in sleep/wakefulness control, especially in shifting animals’ behavioral states from NREM sleep to wakefulness. It also provides an important insight into the pathophysiology of insomnia and the role of orexin in arousal regulation, which will hopefully lead to the first step to develop remedies for sleep disorders,” Sakurai says.
Source: Masataka Sasabe – University of Tsukuba
Image Source: NeuroscienceNews.com image is credited to Univetsity of Tsukuba.
Original Research: Abstract for “Excitation of GABAergic neurons in the bed nucleus of the stria terminalis triggers immediate transition from non-rapid eye movement sleep to wakefulness in mice” by Shota Kodani, Shingo Soya and Takeshi Sakurai in Journal of Neuroscience. Published online June 22 2017 doi:10.1523/JNEUROSCI.0245-17.2017
[cbtabs][cbtab title=”MLA”]University of Tsukuba “The Secret Connection Between Anxiety and Sleep.” NeuroscienceNews. NeuroscienceNews, 3 July 2017.
<https://neurosciencenews.com/sleep-anxiety-7016/>.[/cbtab][cbtab title=”APA”]University of Tsukuba (2017, July 3). The Secret Connection Between Anxiety and Sleep. NeuroscienceNew. Retrieved July 3, 2017 from https://neurosciencenews.com/sleep-anxiety-7016/[/cbtab][cbtab title=”Chicago”]University of Tsukuba “The Secret Connection Between Anxiety and Sleep.” https://neurosciencenews.com/sleep-anxiety-7016/ (accessed July 3, 2017).[/cbtab][/cbtabs]
Abstract
Excitation of GABAergic neurons in the bed nucleus of the stria terminalis triggers immediate transition from non-rapid eye movement sleep to wakefulness in mice
Emotionally salient situations usually trigger arousal along with autonomic and neuroendocrine reactions. To examine whether the extended amygdala plays a role in sleep/wakefulness regulation, we examined the effects of optogenetic and pharmacogenetic excitation of GABAergic neurons in the bed nucleus of the stria terminalis (GABABNST neurons). Acute optogenetic excitation of these cells during non-rapid eye movement (NREM) sleep resulted in immediate state transition to wakefulness, while stimulation during rapid eye movement (REM) sleep showed no effect on sleep/wakefulness states in male mice. Anterograde tracing study suggested GABABNST neurons send axonal projections to several brain regions implicated in arousal, including the preoptic area, lateral hypothalamus, periaqueductal gray, deep mesencephalic nucleus and parabrachial nucleus. A dual orexin receptor antagonist, DORA 22, did not affect the optogenetic transition from NREM sleep to wakefulness. Chemogenetic excitation of GABABNST neurons evoked a sustained wakefulness state, but this arousal effect was markedly attenuated by DORA 22. These observations suggest that GABABNST neurons play an important role in transition from NREM sleep to wakefulness without the function of orexin neurons, but prolonged excitation of these cells mobilizes the orexin system to sustain wakefulness.
SIGNIFICANCE STATEMENT
We examined the role of the bed nucleus of the stria terminalis (BNST) in the regulation of wakefulness. Optogenetic excitation of GABAergic neurons in the BNST (GABABNST neurons) during NREM sleep in mice resulted in immediate transition to a wakefulness state without function of orexins. Prolonged excitation of GABABNST neurons by a chemogenetic method evoked a longer-lasting, sustained wakefulness state, which was abolished by pre-administration of a dual orexin receptor antagonist, DORA 22. This study revealed a role of the BNST GABAergic system in sleep-wakefulness control, especially in shifting animals’ behavioral states from NREM sleep to wakefulness, and provides an important insight into the pathophysiology of insomnia and the role of orexin in arousal regulation.
“Excitation of GABAergic neurons in the bed nucleus of the stria terminalis triggers immediate transition from non-rapid eye movement sleep to wakefulness in mice” by Shota Kodani, Shingo Soya and Takeshi Sakurai in Journal of Neuroscience. Published online June 22 2017 doi:10.1523/JNEUROSCI.0245-17.2017
