The role of monoaminergic neurons in modulating respiration during sleep and the connection with SUDEP

Gu, LeYuan; Yu, Qian; Shen, Yue; Wang, Yuling; Xu, Qianfan; Zhang, Honghai

doi:10.1016/j.biopha.2022.112983

Cited by 8 publications

(5 citation statements)

References 202 publications

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“…Additionally, the identification of wake-active neurons is a necessary step in resolving the mechanism(s) underlying the regulation of wakefulness. For example, monoaminergic neurons in the ascending activating system 38 – 41 and orexin neurons in lateral hypothalamus 42 , 43 have been identified as wake-active neurons that are important for the modulation of wakefulness. Here, using optical fiber and optrode recordings, we found a group of wake-active MS projecting neurons in SuM (Fig.…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic supramammillary neurons that project to the medial septum modulate wakefulness in mice

Liang,

Jian,

Tao

et al. 2023

Commun Biol

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The hypothalamic supramammillary nucleus (SuM) plays a crucial role in controlling wakefulness, but the downstream target regions participating in this control process remain unknown. Here, using circuit-specific fiber photometry and single-neuron electrophysiology together with electroencephalogram, electromyogram and behavioral recordings, we find that approximately half of SuM neurons that project to the medial septum (MS) are wake-active. Optogenetic stimulation of axonal terminals of SuM-MS projection induces a rapid and reliable transition to wakefulness from non-rapid-eye movement or rapid-eye movement sleep, and chemogenetic activation of SuMMS projecting neurons significantly increases wakefulness time and prolongs latency to sleep. Consistently, chemogenetically inhibiting these neurons significantly reduces wakefulness time and latency to sleep. Therefore, these results identify the MS as a functional downstream target of SuM and provide evidence for the modulation of wakefulness by this hypothalamic-septal projection.

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Section: Discussionmentioning

confidence: 99%

Hypothalamic supramammillary neurons that project to the medial septum modulate wakefulness in mice

Liang,

Jian,

Tao

et al. 2023

Commun Biol

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“…The copyright holder for this preprint this version posted December 21, 2022. ; https://doi.org/10.1101/2022.12.20.521335 doi: bioRxiv preprint regulation of wakefulness. For example, monoaminergic neurons in the ascending activating system (Gu et al, 2022;Kayama & Koyama, 2003;Liu & Dan, 2019;Scammell et al, 2017) and orexin neurons in lateral hypothalamus (Lee et al, 2005;Mileykovskiy et al, 2005) have been identified as wake-active neurons that are essential for wakefulness control. Here, using optical fiber and optrode recordings, we found a group of wake-active MS projecting neurons in SuM (Figures 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic supramammillary neurons that project to the medial septum control wakefulness

Liang

Jian

Jin

et al. 2022

Preprint

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The hypothalamic supramammillary nucleus (SuM) plays a key role in controlling wakefulness, but the downstream target regions participating in this control process remain unknown. Here, using circuit-specific fiber photometry and single-neuron electrophysiology together with electroencephalogram, electromyogram and behavioral recordings, we find approximately half of SuM neurons that project to the medial septum (MS) are wake-active. Optogenetic stimulation of axonal terminals of SuM-MS projection induces a rapid and reliable transition to wakefulness from NREM or REM sleep, and chemogenetic activation of SuMMS projecting neurons significantly increases wakefulness time and prolongs latency to sleep. Consistently, chemogenetically inhibiting these neurons significantly reduces wakefulness time and latency to sleep. Therefore, these results identify the MS as a functional downstream target of SuM and provide evidence for a causal role for this hypothalamic-septal projection in wakefulness control.

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“…KET primarily acts on the 5-HT2A receptor, functioning as a 5-HT2A receptor antagonist. Prazosin (Cat #P7791,Sigma-Aldrich,USA), on the other hand, is an NE-α 1R antagonist that blocks the effect of norepinephrine on α1-receptors, and is commonly used for the management and treatment of hypertension, benign prostatic hyperplasia, and posttraumatic stress disorder-related conditions 30 . Both KET and Prazosin were prepared using 25% Dimethylsulfoxide (DMSO).…”

Section: Effect Of Pcpa/dsp-4 On Acoustic Stimulation or Ptz-induced ...mentioning

confidence: 99%

Modulation Of SUDEP By Central Serotonergic Cooperating with Noradrenergic Circuits: A Synergistic-Dependent Manner

Xu,

et al. 2024

Preprint

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Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in refractory epilepsy patients. Despite previous accumulating evidence has shown that seizure-induced respiratory arrest (S-IRA) may play the main contributor to SUDEP as an initiating event preeminent cause of mortality, the specific underlying mechanism of action remains unclear. Based on our previous work, serotonin (5-HT) signaling in the dorsal raphe nucleus (DRN) is strongly implicated in S-IRA in animal models, including the DBA/1 mice, on the meanwhile, norepinephrine (NE) neurons of the locus coeruleus (LC) also plays a vital role in regulating respiratory function on its own. Superficially, monoaminergic neuron, as important neurotransmitters in the central nervous system, have similar modes of action in the maintenance of nervous system balance, and each of them has a regulatory effect on SUDEP. However, it remains to be investigated whether monoaminergic neuron family (NE and 5-HT) are related in the mechanism of regulating SUDEP, what is even more curious is whether the two are intrinsically linked. Thus, we hypothesize neural mechanism of central noradrenergic and serotonergic circuits in modulating SUDEP in a synergistic-dependent manner, this endeavor will culminate in a significant breakthrough in elucidating the precise mechanism of action underlying SUDEP. In our study, we will use chemogenetics, optogenetics, calcium signal recording, and bidirectional tracing to explore the internal mechanism of DR-LC regulating the occurrence of SUDEP, and by specifically injecting 5-HT2AR antagonist Ketanserin (KET) and/or NEα-1R antagonist Prazosin into the pre-Bötzinger complex (PBC), it was finally elucidate that the DR-LC-PBC network can effectively reduce the incidence of SIRA. We firstly proposed a powerful target for exploring the reduction of the incidence of SUDEP, which has great clinical translation potential.

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The role of monoaminergic neurons in modulating respiration during sleep and the connection with SUDEP

Cited by 8 publications

References 202 publications

Hypothalamic supramammillary neurons that project to the medial septum modulate wakefulness in mice

Hypothalamic supramammillary neurons that project to the medial septum modulate wakefulness in mice

Hypothalamic supramammillary neurons that project to the medial septum control wakefulness

Modulation Of SUDEP By Central Serotonergic Cooperating with Noradrenergic Circuits: A Synergistic-Dependent Manner

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