Monoamines Inhibit GABAergic Neurons in Ventrolateral Preoptic Area That Make Direct Synaptic Connections to Hypothalamic Arousal Neurons

Saito, Yuki; Maejima, Takashi; Nishitani, Mitsuhiro; Hasegawa, Emi; Yanagawa, Yuchio; Mieda, Michihiro; Sakurai, Takeshi

doi:10.1523/jneurosci.2835-17.2018

Cited by 63 publications

(56 citation statements)

References 48 publications

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“…Direct serotonergic input to orexin neurons might tonically inhibit orexin neurons during wakefulness states, constituting negative feedback regulation. We also confirmed that optogenetic activation of serotonergic fibers in the LH inhibited orexin neurons in vitro ( Saito et al, 2018 ). Although chemogenetic activation of 5-HT neurons in the DR showed minimal effects on activity of orexin neurons in vivo ( Saito et al, 2018 ), the physiological relevance of direct serotonergic influences on orexin neurons in the regulation of sleep/wakefulness states has been unclear.…”

Section: Discussionsupporting

confidence: 74%

“…Elucidation of the regulatory mechanisms of orexin neurons is important for understanding the physiological mechanisms of sleep/wakefulness control and the roles of orexin neurons in these functions. Orexin neurons receive innervations from many brain regions, including the limbic system, preoptic area, and monoaminergic neurons ( Sakurai et al, 2005 ; Yoshida et al, 2006 ; Saito et al, 2018 ). Among the factors that influence the activity of orexin neurons, serotonin (5-HT) was shown to strongly inhibit most orexin neurons through 5HT 1A receptors (5HT1ARs) ( Muraki et al, 2004 ; Tabuchi et al, 2014 ; Saito et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

“…Orexin neurons receive innervations from many brain regions, including the limbic system, preoptic area, and monoaminergic neurons ( Sakurai et al, 2005 ; Yoshida et al, 2006 ; Saito et al, 2018 ). Among the factors that influence the activity of orexin neurons, serotonin (5-HT) was shown to strongly inhibit most orexin neurons through 5HT 1A receptors (5HT1ARs) ( Muraki et al, 2004 ; Tabuchi et al, 2014 ; Saito et al, 2018 ). At the same time, GABAergic neurons in the preoptic area that send direct inhibitory projections to orexin neurons are inhibited by 5-HT ( Saito et al, 2018 ), implying that the serotonergic regulation of orexin neurons is complex.…”

Section: Introductionmentioning

confidence: 99%

“…Among the factors that influence the activity of orexin neurons, serotonin (5-HT) was shown to strongly inhibit most orexin neurons through 5HT 1A receptors (5HT1ARs) ( Muraki et al, 2004 ; Tabuchi et al, 2014 ; Saito et al, 2018 ). At the same time, GABAergic neurons in the preoptic area that send direct inhibitory projections to orexin neurons are inhibited by 5-HT ( Saito et al, 2018 ), implying that the serotonergic regulation of orexin neurons is complex. A retrograde tracing study of DR 5-HT neurons using rabies virus also showed that orexin neurons send innervations to serotonergic neurons in the DR, suggesting a close relationship between orexin and 5-HT ( Pollak Dorocic et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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Serotonergic Input to Orexin Neurons Plays a Role in Maintaining Wakefulness and REM Sleep Architecture

et al. 2018

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Neurons expressing neuropeptide orexins (hypocretins) in the lateral hypothalamus (LH) and serotonergic neurons in the dorsal raphe nucleus (DR) both play important roles in the regulation of sleep/wakefulness states, and show similar firing patterns across sleep/wakefulness states. Orexin neurons send excitatory projections to serotonergic neurons in the DR, which express both subtypes of orexin receptors (Mieda et al., 2011), while serotonin (5-HT) potently inhibits orexin neurons through activation of 5HT1A receptors (5HT1ARs). In this study, we examined the physiological importance of serotonergic inhibitory regulation of orexin neurons by studying the phenotypes of mice lacking the 5HT1A receptor gene (Htr1a) specifically in orexin neurons (ox5HT1ARKO mice). ox5HT1ARKO mice exhibited longer NREM sleep time along with decreased wakefulness time in the later phase of the dark period. We also found that restraint stress induced a larger impact on REM sleep architecture in ox5HT1ARKO mice than in controls, with a larger delayed increase in REM sleep amount as compared with that in controls, indicating abnormality of REM sleep homeostasis in the mutants. These results suggest that 5HT1ARs in orexin neurons are essential in the regulation of sleep/wakefulness states, and that serotonergic regulation of orexin neurons plays a crucial role in the appropriate control of orexinergic tone to maintain normal sleep/wake architecture.

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Section: Discussionsupporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serotonergic Input to Orexin Neurons Plays a Role in Maintaining Wakefulness and REM Sleep Architecture

et al. 2018

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“…The CSF-contacting nucleus receives input from the LH, PeF, and ZI and may participate in sleeping and arousal. Different neuron types in the tuberomammillary nucleus and LH are implicated in the sleep/wakefulness regulation (Saito et al, 2018). The PeF receives inputs from circadian rhythm messages of the SCh to promote waking (Zhong et al, 2017).…”

Section: Sleeping and Arousalmentioning

confidence: 99%

Monosynaptic Input Mapping of Diencephalic Projections to the Cerebrospinal Fluid-Contacting Nucleus in the Rat

et al. 2020

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Objective: To investigate the projections the cerebrospinal fluid-contacting (CSFcontacting) nucleus receives from the diencephalon and to speculate on the functional significance of these connections. Methods:The retrograde tracer cholera toxin B subunit (CB) was injected into the CSF-contacting nucleus in SD rats according to the experimental formula of the stereotaxic coordinates. Animals were perfused 7-10 days after the injection, and the diencephalon was sliced at 40 µm with a freezing microtome. CB-immunofluorescence was performed on all diencephalic sections. The features of CB-positive neuron distribution in the diencephalon were observed with a fluorescence microscope. Results:The retrograde labeled CB-positive neurons were found in the epithalamus, subthalamus, and hypothalamus. Three functional diencephalic areas including 43 sub-regions revealed projections to the CSF-contacting nucleus. The CB-positive neurons were distributed in different density ranges: sparse, moderate, and dense.Conclusion: Based on the connectivity patterns of the CSF-contacting nucleus that receives anatomical inputs from the diencephalon, we preliminarily assume that the CSF-contacting nucleus participates in homeostasis regulation, visceral activity, stress, emotion, pain and addiction, and sleeping and arousal. The present study firstly illustrates the broad projections of the CSF-contacting nucleus from the diencephalon, which implies the complicated functions of the nucleus especially for the unique roles of coordination in neural and body fluids regulations.

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Intermittent Vibration Induces Sleep via an Allatostatin A‐GABA Signaling Pathway and Provides Broad Benefits in Alzheimer's Disease Models

Mou,

Zhang,

Zheng

et al. 2024

Advanced Science

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While animals across species typically experience suppressed consciousness and an increased arousal threshold during sleep, the responsiveness to specific sensory inputs persists. Previous studies have demonstrated that rhythmic and continuous vibration can enhance sleep in both animals and humans. However, the neural circuits underlying vibration‐induced sleep (VIS) and its potential therapeutic benefits on neuropathological processes in disease models remain unclear. Here, it is shown that intermittent vibration, such as cycles of 30 s on followed by 30 s off, is more effective in inducing sleep compared to continuous vibration. A clear evidence is further provided that allatostatin A (AstA)‐GABA signaling mediates short‐term intermittent vibration‐induced sleep (iVIS) by inhibiting octopaminergic arousal neurons through activating GABAA receptors. The existence of iVIS in mice is corroborated, implicating the GABAergic system in this process. Finally, intermittent vibration not only enhances sleep but also reduces amyloid‐β (Aβ) deposition and reverses memory defects in Alzheimer's disease models. In conclusion, the study defines a central neural circuit involved in mediating short‐term iVIS and the potential implications of vibration in treating sleep‐related brain disorders.

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Monoamines Inhibit GABAergic Neurons in Ventrolateral Preoptic Area That Make Direct Synaptic Connections to Hypothalamic Arousal Neurons

Cited by 63 publications

References 48 publications

Serotonergic Input to Orexin Neurons Plays a Role in Maintaining Wakefulness and REM Sleep Architecture

Serotonergic Input to Orexin Neurons Plays a Role in Maintaining Wakefulness and REM Sleep Architecture

Monosynaptic Input Mapping of Diencephalic Projections to the Cerebrospinal Fluid-Contacting Nucleus in the Rat

Intermittent Vibration Induces Sleep via an Allatostatin A‐GABA Signaling Pathway and Provides Broad Benefits in Alzheimer's Disease Models

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