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Whole-Brain Monosynaptic Inputs to Hypoglossal Motor Neurons in Mice

Neuroscience Bulletin 2020年第6期36卷 585-597页

作者： Han Guo Xiang-Shan Yuan Ji-Chuan Zhou Hui Chen Shan-qun Li wei-min qu Zhi-Li Huang Department of Pharmacology School of Basic Medical SciencesState Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceInstitutes of Brain ScienceFudan UniversityShanghai 200032China Department of Anatomy School of Basic Medical SciencesFudan UniversityShanghai 200032China Department of Pulmonary Medicine Zhongshan HospitalFudan UniversityShanghai 200032China

Hypoglossal motor neurons(HMNs) innervate tongue muscles and play key roles in a variety of physiological functions,including swallowing,mastication,suckling,vocalization,and respiration.Dysfunction of HMNs is associated with several diseases,such as obstructive sleep apnea(OSA) and sudden infant death syndrome.OS A is a serious breathing disorder associated with the activity of HMNs during different sleep-wake states.Identifying the neural mechanisms by which the statedependent activities of HMNs are controlled may be helpful in providing a theoretical basis for effective therapy for OSA.However,the presynaptic partners governing the activity of HMNs remain to be elucidated.In the present study,we used a cell-type-specific retrograde tracing system based on a modified rabies virus along with a Cre/loxP gene-expression strategy to map the whole-brain monosynaptic inputs to HMNs in mice.We identified 53 nuclei targeting HMNs from six brain regions:the amygdala,hypothalamus,midbrain,pons,medulla,and cerebellum.We discovered that GAB Aergic neurons in the central amygdaloid nucleus,as well as calretinin neurons in the parasubthalamic nucleus,sent monosynaptic projections to HMNs.In addition,HMNs received direct inputs from several regions associated with respiration,such as the preBotzinger complex,parabrachial nucleus,nucleus of the solitary tract,and hypothalamus.Some regions engaged in sleep-wake regulation(the parafacial zone,parabrachial nucleus,ventral medulla,sublaterodorsal tegmental nucleus,dorsal raphe nucleus,periaqueductal gray,and hypothalamus) also provided primary inputs to HMNs.These results contribute to further elucidating the neural circuits underlying disorders caused by the dysfunction of HMNs.

关键词： Hypoglossal motor neuron Monosynaptic input Rabies virus Respiration Sleep and wake

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Neural circuits of basal ganglia in sleep-wake regulation

Neural circuits of basal ganglia in sleep-wake regulation

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中国睡眠研究会第十四届全国学术年会

作者： wei-min qu Zhi-Li Huang School of Basic Medical Sciences Fudan University

Objective The basal ganglia(BG) act as a cohesive functional unit that regulates motor function, habit formation, and reward/addictive behaviors. Patients with Parkinson’s disease suffer from severe sleep disorders. However, the roles a of the BG in controlling sleep-wake cycles remain unknown. Methods We used fiber photometry, multichannel electrophysiological recordings and genetic approaches to determine the roles and neuron circuits of BG in the sleep-wake regulation in mice. Results We found that optogenetic activation of A2AR expressing neurons in the nucleus accumbens(NAc) increased non-rapid eye movement(NREM) sleep. Projections of A2AR neurons from the NAc distributed to nuclei in the forebrain, diencephalon, and brainstem. Moreover, chemogenetic activation of A2AR neurons in the rostral and central dorsal striatum, but not caudal, induced remarkable increase in NREM sleep through inhibition of parvarlbumin-positive neurons in the external globus pallidus(GPe). In contrast, optogenetic activation of NAc or dorsal striatal D1R neurons promoted wakefulness. Conversely, chemogenetic inhibition of D1R neurons attenuated wakefulness. NAc D1R neurons projected to non-dopamine neurons in the midbrain for control of wakefulness. The activity of dorsal striatal D1R neurons is the highest during wakefulness and is highly synchronized with and regulated by afferent corticostriatal and thalamostriatal neurons. Conclusion The dorsal striatum and the nucleus accumbens integrate behavioral processes with sleep/wakefulness through adenosine and dopamine receptors.

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Keeping the right time in space: importance of circadian clock and sleep for physiology and performance of astronauts

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Journal of Medical Colleges of PLA(China) 2014年第3期29卷 143-146,147,144页

作者： Jin-Hu Guo wei-min qu Shan-Guang Chen Xiao-Ping Chen Ke Lv Zhi-Li Huang Yi-Lan Wu Key Laboratory of Gene Engineering of the ministry of Education State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University Department of Pharmacology School of Basic Medical Sciences Fudan University National Key Laboratory of Human Factors Engineering China Astronaut Research and Training Center State Key Laboratory of Space Medicine Fundamentals and Application China Astronaut Research and Training Center

The circadian clock and sleep are essential for human physiology and behavior; deregulation of circadian rhythms impairs health and performance. Circadian clocks and sleep evolved to adapt to Earth's environment, which is characterized by a 24-hour light–dark cycle. Changes in gravity load, lighting and work schedules during spaceflight missions can impact circadian clocks and disrupt sleep, in turn jeopardizing the mood, cognition and performance of orbiting astronauts. In this review, we summarize our understanding of both the influence of the space environment on the circadian timing system and sleep and the impact of these changes on astronaut physiology and performance.

关键词： Space Circadian rhythm Sleep Performance Counterme

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Parasubthalamic calretinin neurons are essential in the control of wakefulness associated with exploration in mice

Parasubthalamic calretinin neurons are essential in the cont...

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中国睡眠研究会第十四届全国学术年会

作者： Han Guo Jian-bo Jiang Shan-qun Li Zhi-li Huang wei-min qu Fudan University

The parasubthalamic nucleus(PSTN) is considered to be related to motivation, feeding, and hunting, all of which are highly dependent on wakefulness. However, the role and underlying neural circuits of the PSTN in wakefulness remain unclear. Calretinin(CR), a member of a large family of cytoplasmic calcium-binding proteins, is relatively specifically expressed in PSTN neurons, and CR neurons account for the majority of PSTN neurons. In this study, fiber photometry recordings showed that the activity of PSTNCR neurons increased at the transitions from non-rapid eye movement(non-REM, NREM) sleep to either wakefulness or REM sleep, as well as exploratory behavior such as sniffing, rearing, and walking. Chemogenetic activation of PSTNCR neurons prolonged wakefulness together with increased sniffing and rearing behavior, center time in the open-field test(OFT), and the number of entries into the light box. Moreover, optogenetic stimulation of PSTNCR neurons induced immediate transitions from NREM sleep to wakefulness, and increased the center time in the OFT. The photoactivation of projections of PSTNCR neurons in the ventral tegmental area(VTA) and parabrachial nucleus(PB), but not in the paraventricular thalamus(PVT), promoted arousal. The wakefulness evoked by the PSTNCR-VTA pathway was accompanied by increased center time in the OFT. Moreover, inhibition of PSTNCR neurons suppressed arousal, resulting in decreased sniffing, rearing, and walking behaviors. Collectively, our findings indicate that PSTNCR circuitry plays a fundamental role in the induction and maintenance of the awake state associated with exploration through the PSTNCR-VTA pathway.

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Whole-Brain Monosynaptic Afferents to Rostromedial Tegmental Nucleus Gamma-Aminobutyric Acid-Releasing Neurons in Mice

Whole-Brain Monosynaptic Afferents to Rostromedial Tegmental...

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中国睡眠研究会第十四届全国学术年会

作者： Su-Rong Yang Ya-Nan Zhao Yang Zhang Shi-Yuan Tao Zhi-Li Huang wei-min qu Department of Pharmacology School of BaMedical Sciences State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science

Increasing evidence has revealed that the rostromedial tegmental area(RMTg) mediates many behaviors, including sleep and addiction. However, presynaptic patterns governing the activity of γ-aminobutyric acid-releasing(GABAergic) neurons, the main neuronal type in the RMTg, have not been defined. Here, we used cell-type-specific retrograde trans-synaptic rabies viruses to map and quantify the monosynaptic afferents to RMTg GABAergic neurons in mouse whole brains. We identified 71 ascending projection brain regions. Sixtyeight percent of the input neurons arise from the ipsilateral and 32% from the contralateral areas of the brain. The first three strongest projection regions were the ipsilateral lateral hypothalamus, zone incerta, and contralateral pontine reticular nucleus. Immunohistochemistry imaging showed that the input neurons in the dorsal raphe, laterodorsal tegmentum, and dorsal part of zone incerta were colocalized with serotoninergic, cholinergic, and neuronal nitric oxide synthetase-expressing neurons, respectively. However, in the lateral hypothalamus, a few input neurons innervating RMTg GABAergic neurons colocalized orexinergic neurons but lacked colocalization of melanin-concentrating hormone neurons. Our findings provide anatomical evidence to understand how RMTg GABAergic neurons integrate diverse information to exert varied functions.

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Sleep-wake characteristics in a rat model of autism spectrum disorder with complete Shank3 deletion

Sleep-wake characteristics in a rat model of autism spectrum...

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中国睡眠研究会第十四届全国学术年会

作者： Gui-Jin Tao Pei-Wen Song wei-min qu Rong Zhang Zhi-Li Huang Mei-Hong Qiu Fudan University Department of Pharmacology School of Basic Medical Science State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan University Department of Neurobiology School of Basic Medical Sciences Peking University

The synaptic gene Shank3 is a high confidence candidate gene for autism spectrum disorder(ASD). We previously reported a new line of Shank3 mutant rat which results in a complete loss of Shank3 by deleting exons 11-21(Δe11-21) globally. The Shank3Δe11-21 rats display obvious ASD-like behaviors and abnormal pain and thermal sensation, which mimic the symptoms of patients with Shank3 mutations. Since ASD strikes early in life, moreover it is often co-presenting with sleep problems, which can predict the severity of ASD core symptoms and may worsen the symptoms of the disease, here we further investigated the effect of shank3 deficiency on sleep architecture in juvenile rats, to better understand the biological characteristics of the Shank3Δe11-21 rats. Spontaneously locomotor activity and EEG/EMGs of the rats were recorded at postnatal day 23 and 30-31, respectively. We found that although male juvenile Shank3-/-rats displayed hypoactivity, they spent less time in NREM sleep during the dark period. The sleep profile of female juvenile Shank3-/-rats were similar to those of males, while they slept less during both the dark and light period, and the amount of REM sleep in dark phase was also significantly decreased. Further in-depth analysis of the duration of sleep-wake episodes revealed that the male juvenile Shank3-/-rats exhibited sleep fragmentation, as manifested by an increase in short wake bouts. Instead, the increase of wakefulness in the female juvenile Shank3-/-rats was mainly due to their longer duration of wakefulness episodes. EEG power spectra analysis showed that both male and female juvenile Shank3-/-rats exhibited reduced sleep intensity. Overall, our study shows that Shank3 deficiency causes sleep disturbances in rats at an early age. Together with the results of our previous behavior studies, this new rat model well presented the behavioral phenotypes associated with ASD comorbidities, which will facilitate to further promote the research for proper understanding of Shank3 related neurodevelopment

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A Path Planning Algorithm Based on Typical Case Reasoning

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Geo-Spatial Information Science 2009年第1期12卷 66-71页

作者： WENG min wei Xiuqin qu Rong CAI Zhongliang School of Resource and Environment Science Wuhan University129 Luoyu Road Wuhan 430079 China

基于盒子的推理是以前的答案在被存储为未来使用的一种 AI 技术。人们习惯于根据在他们的记忆被存储并且以前被他们使用了的那些线路指导自己。只基于人到熟悉的线路的偏爱，它通过认知活动的学习被获得。我们建议基于推理到路径计划的... 详细信息

基于盒子的推理是以前的答案在被存储为未来使用的一种 AI 技术。人们习惯于根据在他们的记忆被存储并且以前被他们使用了的那些线路指导自己。只基于人到熟悉的线路的偏爱，它通过认知活动的学习被获得。我们建议基于推理到路径计划的盒子使用聪明的方法。一个盒子底存储所有答案到所有最短的路径是不可能的；因此，他们的部分应该被存储。不管多么，线路哪个并且哪个应该被存储不应该是？我们怎么并且怎么改编已经被存储了的盒子我们基于他们获得最短的线路？所有这些问题需要被由于基于盒子的推理技术，集成网络的知识解释。这篇论文建议在另一个点的基于盒子的推理。根据问题空间的总分析发现一些不能替代的连接的这个工具，它被称为 must_be_passed 在来源和目的地之间连接。仅仅从格子的那些最好的出口 / 入口节点计算最短的路径盒子到不能替代的连接，然后增加他们进存储为未来使用的盒子底。这个方法基于基于盒子的推理技术并且完全考虑问题空间的性质。除了在线路网络的自然格子的知识的使用，这个方法是比计算效率上的存在算法更有效的。

关键词：典型事例推理路径规划方法智能技术

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Alleviating sleep disturbances and modulating neuronal activity after ischemia: Evidence for the benefits of zolpidem in stroke recovery

Alleviating sleep disturbances and modulating neuronal activ...

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中国睡眠研究会第十五届全国学术年会

作者： Zhi-Gang Zhong Gui-Jin Tao Shu-Mei Hao Hui Bi wei-min qu Zhi-Li Huang Mei-Hong Qiu School of Basic Medical Sciences Fudan University

Aims: Sleep disorders are prevalent among stroke survivors and impede stroke recovery, yet they are still insufficiently considered in the management of stroke patients, and the mechanisms by which they occur remain unclear.There is evidence that boosting phasic GABA signaling with zolpidem during the repair phase improves stroke recovery by enhancing neural plasticity;however, as a nonbenzodiazepine hypnotic, the effects of zolpidem on post-stroke sleep disorders remain unclear.Method: Transient ischemic stroke in male rats was induced with 30-minute middle cerebral artery occlusion.Zolpidem or vehicle was intraperitoneally delivered once daily from 2 to 7 days after the stroke, and the electroencephalogram and electromyogram were recorded simultaneously.At 24 hours after ischemia, c-Fos immunostaining was used to assess the effect of transient ischemic stroke and acute zolpidem treatment on neuronal activity.Results: In addition to the effects on reducing brain damage and mitigating behavioral deficits, repeated zolpidem treatment during the subacute phase of stroke quickly ameliorated circadian rhythm disruption, alleviated sleep fragmentation, and increased sleep depth in ischemic rats.Immunohistochemical staining showed that in contrast to robust activation in para-infarct and some remote areas by 24 h after the onset of focal ischemia, the activity of the ipsilateral suprachiasmatic nucleus, the biological rhythm center, was strongly suppressed.A single dose of zolpidem significantly upregulated c-Fos expression in the ipsilateral suprachiasmatic nucleus to levels comparable to the contralateral side.Conclusion: Stroke leads to suprachiasmatic nucleus dysfunction.Zolpidem restores suprachiasmatic nucleus activity and effectively alleviates post-stroke sleep disturbances, indicating its potential to promote stroke recovery.

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Optimization on crystallization process of the magnetic core lysozyme

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Particuology 2024年第4期87卷 106-113页

作者： Lixia Hou Chunxiao qu min Su Zhihan Liang Qi Hao School of Chemical Engineering Hebei University of TechnologyTianjin300130China

The continuous growth of the biomedical market highlights the significance of improvement in the ef-ficiency of batch production for protein drug crystals.Herein,we investigated the effect of polymer-modified Fe_(3)O_(4) nanoparticles on lysozyme(Lys)crystallization at different conditions,using function-alized Fe_(3)O_(4) magnetic nanoparticles(Polymer C@Fe_(3)O_(4))as nucleation agents.The study revealed that the surface charge density of Polymer C@Fe_(3)O_(4) was highest at a modification mass ratio of Fe_(3)O_(4) to Polymer C is 8∶3.This ratio facilitates the augmentation of electrostatic interaction and the promotion of crys-tallization.By adding 15%of the PolymerC@Fe_(3)O_(4) prepared from Fe_(3)O_(4) with an average particle size of 150 nm,the magnetic core lysozyme(M-Lys)crystals with an average particle size of 11.08μm,narrow size distribution,and regular morphology were obtained in a yield of 82.42%within 60 min.

关键词： Protein Crystallization Magnetic particle Lysozyme

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Dopamine D2 receptor and sleep-wake regulation

Dopamine D2 receptor and sleep-wake regulation

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中国神经科学学会第十届全国学术会议

作者： Zhi-Li Huang wei-min qu Department of Pharmacology Shanghai Medical CollegeFudan University State Key Laboratory of Medical Neurobiology Shanghai Medical CollegeFudan University The Institute of Brain Science Shanghai Medical CollegeFudan University

Dopamine(DA) has been reported to regulate processes responsible for the generation of complex movements and emotions,cognition,reward processing,and drug addiction.However,the role assigned to DA in sleep-wake regulation has been relatively limited.The main DA receptors(R) in the brain are DR and DR.To clarify the roles of DA receptors in the sleep-wake regulation,DR knock-out(KO) mice,selective gene deletion strategies based on focal RNA interference to silence the expression of DR,the human DR gene carried by AAV to focally rescue DR in DR KO mice,and pharmacological manipulation were used.We found that the DR blockade could reduce the sleep latency and increase amounts of non-rapid eye movement(non-REM,NREM) sleep.Modafinil is the most potent wake-promoting medicine for enhancing the extracellular DA level in the nucleus accumbens and the prefrontal cortex,and for increasing wakefulness.By using DR KO mice and DR antagonist,we demonstrated that DR and DR are essential for the arousal effect of modafinil,with DR being the receptor of primary importance.Compared with wild-type(WT) mice,DR KO mice exhibited a significant decrease in wakefulness.When the KO mice were subjected to a cage change,the latency to sleep in the KO mice decreased to half of the level for WT mice.Recently,focal RNA interference in WT mice and rescue technology for DR in the KO mice showed that DRs located in the core of NAc play more important role in promoting arousal and locomotion than other parts in the striatum.These results indicate that DR plays an essential role in the maintenance of wakefulness.

关键词： dopamine D2 receptors sleep wakefulness AAV knockout

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