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How do lateral septum projections to the ventral CA1 influence sociability?

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Neural Regeneration Research 2024年第8期19卷 1789-1801页

作者： Dan Wang Di Zhao Wentao Wang Fengai Hu Minghu Cui Jing Liu Fantao Meng Cuilan Liu Changyun Qiu Dunjiang Liu Zhicheng Xu Yameng Wang Yu Zhang Wei Li Chen Li Department of Rehabilitation Medicine Binzhou Medical University HospitalBinzhouShandong ProvinceChina Medical Research Center Binzhou Medical University HospitalBinzhouShandong ProvinceChina Institute for Metabolic&Neuropsychiatric Disorders Binzhou Medical University HospitalBinzhouShandong ProvinceChina Department of Psychology Binzhou Medical University HospitalBinzhouShandong ProvinceChina College of Nursing Binzhou Medical UniversityBinzhouShandong ProvinceChina

Social dysfunction is a risk factor for several neuropsychiatric illnesses.Previous studies have shown that the lateral septum(LS)-related pathway plays a critical role in mediating social behaviors.Howeve r,the role of the connections between the LS and its downstream brain regions in social behavio rs remains unclea r.In this study,we conducted a three-chamber test using electrophysiological and chemogenetic approaches in mice to determine how LS projections to ventral CA1(vCA1)influence sociability.Our res ults showed that gamma-aminobutyric acid(GABA)-e rgic neuro ns were activated following social experience,and that social behavio rs were enhanced by chemogenetic modulation of these neurons.Moreover,LS gabaergic neurons extended their functional neural connections via vCA1 glutamatergic pyramidal neurons,and regulating LSGABA→vCA1Gluneural projections affected social behaviors,which were impeded by suppressing LSprojecting vCA1 neuronal activity or inhibiting GABAAreceptors in vCA1.These findings support the hypothesis that LS inputs to the vCA1 can control social prefe rences and social novelty behaviors.These findings provide new insights rega rding the neural circuits that regulate sociability.

关键词： chemogenetics GABA receptor gabaergic neurons glutamatergic neurons lateral septum neural excitability neural projection social novelty social preference ventral CA1

Melatonin improves synapse development by PI3K/Akt signaling in a mouse model of autism spectrum disorder

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Neural Regeneration Research 2024年第7期19卷 1618-1624页

作者： Luyi Wang Man Xu Yan Wang Feifei Wang Jing Deng Xiaoya Wang Yu Zhao Ailing Liao Feng Yang Shali Wang Yingbo Li Institute of Neuroscience Department of PhysiologySchool of Basic Medical ScienceChongqing Medical UniversityChongqingChina Department of Pediatric Chongqing University Fuling HospitalChongqingChina Department of Neurosurgery Xinqiao HospitalArmy Medical UniversityChongqingChina Department of Pathology Affiliated Hospital of North Sichuan Medical CollegeNanchongSichuan ProvinceChina NHC Key Laboratory of Birth Defects and Reproductive Health Chongqing Population and Family Planning Science and Technology Research InstituteChongqingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina

Autism spectrum disorders are a group of neurodevelopmental disorders involving more than 1100 genes,including Ctnnd2 as a candidate gene.Ctnnd2knockout mice,serving as an animal model of autis m,have been demonstrated to exhibit decreased density of dendritic spines.The role of melatonin,as a neuro hormone capable of effectively alleviating social interaction deficits and regulating the development of dendritic spines,in Ctnnd2 deletion-induced nerve injury remains unclea r.In the present study,we discove red that the deletion of exon 2 of the Ctnnd2 gene was linked to social interaction deficits,spine loss,impaired inhibitory neurons,and suppressed phosphatidylinositol-3-kinase(PI3K)/protein kinase B(Akt) signal pathway in the prefrontal cortex.Our findings demonstrated that the long-term oral administration of melatonin for 28 days effectively alleviated the aforementioned abnormalities in Ctnnd2 gene-knockout mice.Furthermore,the administration of melatonin in the prefro ntal cortex was found to improve synaptic function and activate the PI3K/Akt signal pathway in this region.The pharmacological blockade of the PI3K/Akt signal pathway with a PI3K/Akt inhibitor,wo rtmannin,and melatonin receptor antagonists,luzindole and 4-phenyl-2-propionamidotetralin,prevented the melatonin-induced enhancement of gabaergic synaptic function.These findings suggest that melatonin treatment can ameliorate GABAe rgic synaptic function by activating the PI3K/Akt signal pathway,which may contribute to the improvement of dendritic spine abnormalities in autism spectrum disorders.

关键词： autism Ctnnd2 deletion gabaergic neurons melatonin PI3K/Akt signal pathway prefrontal cortex social behavior spine density synaptic-associated proteins

Whole-Brain Mapping of Direct Inputs to and Axonal Projections from gabaergic neurons in the Parafacial Zone

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Neuroscience Bulletin 2018年第3期34卷 485-496页

作者： Yun-Ting Su Meng-Yang Gu Xi Chu Xiang Feng Yan-Qin Yu Department of Neurobiology and Physiology Key Laboratory of Medical Neurobiology of the Ministry of Health Key Laboratory of Neurobiology Zhejiang University School of Medicine Department of Medicine Zhejiang University School of Medicine

The gabaergic neurons in the parafacial zone（PZ） play an important role in sleep-wake regulation and have been identified as part of a sleep-promoting center in the brainstem, but the long-range connections mediating this function remain poorly characterized. Here, we performed whole-brain mapping of both the inputs and outputs of the gabaergic neurons in the PZ of the mouse brain. We used the modified rabies virus Env A-DG-Ds Red combined with a Cre/lox P gene-expression strategy to map the direct monosynaptic inputs to the gabaergic neurons in the PZ, and found that they receive inputs mainly from the hypothalamic area, zona incerta, and parasubthalamic nucleus in the hypothalamus; the substantia nigra, pars reticulata and deep mesencephalic nucleus in the midbrain;and the intermediate reticular nucleus and medial vestibular nucleus（parvocellular part） in the pons and medulla.We also mapped the axonal projections of the PZ gabaergic neurons with adeno-associated virus, and defined the reciprocal connections of the PZ gabaergic neurons with their input and output nuclei. The newlyfound inputs and outputs of the PZ were also listed compared with the literature. This cell-type-specific neuronal whole-brain mapping of the PZ gabaergic neurons may reveal the circuits underlying various functions such as sleep-wake regulation.

关键词： Parafacial zone Parvocellular reticular formation gabaergic neurons Trans-synaptic tracing

The Superior Colliculus:Cell Types,Connectivity,and Behavior

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Neuroscience Bulletin 2022年第12期38卷 1519-1540页

作者： Xue Liu Hongren Huang Terrance PSnutch Peng Cao Liping Wang Feng Wang Shenzhen Key Lab of Neuropsychiatric Modulation Guangdong Provincial Key Laboratory of Brain Connectome and BehaviorCAS Key Laboratory of Brain Connectome and Manipulationthe Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhen 518055China University of Chinese Academy of Sciences Beijing 100049China Michael Smith Laboratories and Djavad Mowafaghian Centre for Brain Health University of British ColumbiaVancouver V6T 1Z4Canada National Institute of Biological Sciences Beijing 100049China

The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across vertebrate evolution.Moreover,cell-type-specific SC neurons integrate afferent signals within local networks to generate defined output related to innate and cognitive behaviors.This review focuses on the recent progress in understanding of phenotypic diversity amongst SC neurons and their intrinsic circuits and long-projection targets.We further describe relevant neural circuits and specific cell types in relation to behavioral outputs and cognitive functions.The systematic delineation of SC organization,cell types,and neural connections is further put into context across species as these depend upon laminar architecture.Moreover,we focus on SC neural circuitry involving saccadic eye movement,and cognitive and innate behaviors.Overall,the review provides insight into SC functioning and represents a basis for further understanding of the pathology associated with SC dysfunction.

关键词： Superior colliculus Glutamatergic neurons gabaergic neurons Neuronal circuits Innate behaviors

Identified gabaergic System in the Parvocellular Reticular Nucleus Induces Immediate Sleep

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Identified GABAergic System in the Parvocellular Reticular N...

中国睡眠研究会第九届学术年会

作者： Yong Han Yun-ting Su Zheng-gang Zhu Jun-hua Yang Yu-feng Shi Zhi-li Huang Shumin Duan Yan-qin Yu Department of Neurobiology and Physiology Key Laboratory of Medical Neurobiology of Ministry of HealthKey Laboratory of NeurobiologyZhejiang University School of Medicine Department of Pharmacology Shanghai Medical CollegeFudan University

A relatively small number of sleep-promoting nuclei exist in the brain.The parafacial zone was recently identified as a sleep-promoting center in the brainstem.However,little is known about therole of gabaergic neurons in its subnucleus-the parvocellular reticular nucleus（PCRtA） in sleepwake behavior.Here,we found the vesicular GABA transporter（VGAT）-ChR2-EYFP mice showed a significant increase of Fos-positive gabaergic neurons in the PCRtA after they were activated by photostimulation in vivo.Optical activation of gabaergic PCRtA neurons promoted the transition from wakefulness to slow-wave sleep（SWS） rather than rapid-eye-movement（REM） sleep,or extended SWS when the animal was already in SWS.Activation of gabaergic neurons in the PCRtA generated a slow wave in REM sleep,but did not change REM sleep itself.Using an optetrode,we classified the spontaneous firing of PCRtA neurons into 3 subpopulations:firing maximally in SWS,in REM sleep,or in wakefulness.The firing of gabaergic PCRtA neurons during photostimulation increased in VGAT-ChR2-EYFP mice.This is the first study to optogenetically stimulate a subset of neurons in a nucleus that generates instantaneous SWS,and the first study showing that a subnucleusin parafacial zone is also a sleep-promoting nucleus.

关键词： the parvocellular reticular nucleus gabaergic neurons optogenetics

The birthdates of GAB Aergic neurons in the mouse spinal cord

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The birthdates of GAB Aergic neurons in the mouse spinal cor...

中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Jing HUANG Jing CHEN Wen WANG Ya-Yun WANG Wei WANG Yun-Qing LI Sheng-Xi WU~* Department of Anatomy and K.K.Leung Brain Research Centre Faculty of Basic Medicine Fourth Military Medical University Xi’an 710032 China

＜正＞Objective Despite the abundance of studies on gabaergic neurons distribution in the mouse developing spinal cord,no investigation has been devoted so far to the birthdates of gabaergic neurons.Methods In order to determine the spinal neurogenesis of a specific phenotype,the gabaergic neurons in the spinal cord,we injected bromodeoxyuridine（BrdU） at different stages during development and labeled spinal sections for GABA immunocytochemistry at a specific day,60 days after birth.The glutamic acid decarboxylase（GAD）67-green fluorescent protein （GFP） knock-in mouse was used in which all gabaergic neurons were fluorescent.We labeled newly born cells with the S-phase marker BrdU and used GFP to characterize gabaergic neurons at different time points after cell division.Results Birthdating studies revealed that gabaergic neurogenesis was present since E10.5.Then the generation of gabaergic neurons significantly increased,reaching a peak at E11.5.The two waves for the co-localization of GABA and BrdU in the spinal cord were seen at E11.5 and E13.5.The vast majority of gabaergic neurons were generated before E14.5.Following, GABA-positive neuron generation decreased drastically.The birthdates of gabaergic neurons in each lamina were different.Conclusion The present results suggest that the birthdates of gabaergic neurons vary and follow a specific temporal sequence.The precise birthdating pattern of gabaergic neurons will provide more information for future functional studies.

关键词： gabaergic neurons BrdU birthdate spinal cord mouse

Estazolam reverses histamine in tuberomammillary nucleus induced arousal effect

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Estazolam reverses histamine in tuberomammillary nucleus ind...

中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Yi-Na SUN Xin ZHANG Xu-Guang YANG Yan-Feng SONG Yi-Ping HOU~* Department of Neuroscience and Anatomy Histology and Embryology School of Basic Medical Sciences Lanzhou University Lanzhou 730000 China

＜正＞Objective The effect of estazolam,a potential agonist for promoting gamma-aminobutyric acid（GABA） release, on histamine（HA） in tuberomammillary nucleus（TMn） induced arousal activity was investigated.The interaction between TMn histaminergic and gabaergic neurons for modulating sleep-wakefulness cycle was further studied.Methods 30 male Sprague-Dawley rats were randomly divided into 6 groups:control group,saline group,sstazolam group,HA group,HA+estazolam（2.5 mg/kg） group,HA+estazolam（5 mg/kg） group.Four stainless steel screw electrodes（2 mm in diameter） were implanted into the skull to the surface of the cerebral dura mater for recording EEG.Two silver wire electrodes were inserted bilaterally into the dorsal neck muscles for recording EMG.The stainless steel guide cannular （0.06 mm in diameter） was implanted into the adjacent of TMn for subsequent drug microinjection.After 7 d recovery,a basic sleep-wake cycle as control of EEG and EMG were recorded and every phase analyzed for 24 h.The wake and sleep states including light slow wave sleep（SWS1）,deep slow wave sleep（SWS2） and paradoxical sleep（PS） were statistically calculated per 10 s epochs for 24 h,when saline and drugs were subsequently administered according to protocol.Results Microinjection HA（1μg/kg） into TMn increased the durational time of wake（P＜0.01） and reduced the S WS time,but did not effect on PS compared to saline microinjection into TMn for 24 h.Estazolam（5 mg/kg,p.o） increased the total sleep time via increase of SWS2（P＜0.01） without SWS1 and PS time compared to control,and also reversed the HA-induced wakefulness into sleep（P＜0.01）.Conclusion Histaminergic neurons in the TMn play a key role in promoting and maintaining the wakefulness.Estazolam induces an increase of the total sleep time,mainly through increasing SWS2,and reverses HA-induced wakefulness into sleep.

关键词： sleep-wakefulness cycle tuberomammillary nucleus histaminergic neurons estazolam gabaergic neurons

Effect of microinjecting GABAA-receptor antagonist into the tuberomammillary nucleus on the sleep-wakefulness cycle after lesion of the ventrolateral preoptic area in rats

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Effect of microinjecting GABAA-receptor antagonist into the ...

中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Xin ZHANG,Yi-Na SUN,Peng XIE,Xu-Guang YANG,Yi-Ping HOU~* Department of Neuroscience and Anatomy,Histology and Embryology,School of Basic Medical Sciences,Lanzhou University,Lanzhou 730000

Objective Recent evidences have demonstrated that the interaction between gabaergic neurons in the ventrolateral preoptic area(VLPO) and histaminergic(HA) neurons in the tuberomammillary nucleus(TMn) plays a key role for regulating sleep-wakefulness cycle.However,gabaergic neurons in TMn have not received much attention for their role in sleep-wakefulness cycle.The aim of this study is to investigate the effect of gabaergic neurons in the TMn on sleep-wakefulness cycle.Methods Male SD rats(250-300 g,n=15) were randomized into 3 groups:before lesion group (n=5),VLPO lesion group(n=5) and VLPO lesion plus bicuculline treated group(n=5).The 4 EEG screw electrodes were implanted into the skull under anesthesia with pentobarbital(35 mg/Kg,ip),and three flexible EMG wire electrodes were placed into the nechal muscles.The free ends of the leads were soldered into a socket.Guide cannular for microinjection were implanted into the adjacent of TMn(Aβ-4.2 mm,ML±1.3 mm,DV-7.4 mm).All implantations were affixed to the skull with dental cement,except the area(0.5 cm) around the bregma filling with bone wax that was removable.One week after surgery,the sockets were connected via flexible recording cables to EEG polygraph,signals were digitized by CED Micro 1401 and computer running the Spike 2 recording system.A 24 h basic wake-sleep states in before lesion group were recorded and analyzed by manually scored in 30 s epochs on the digitized EEG/EMG.On the 8th day,a fine glass micropipette(10-20 mm tip diameter) containing ibotenic acid solution for specific cell damage(10 nM/0.5μ,Sigma) was injected into the VLPO on each side after bone wax removed under anesthetization.One week after the second surgery,rats of VLPO lesion group were recorded for sleep-wakefulness states.On the 10th day after lesion of VLPO,bicuculline(10 nM/0.5μ),a GABA-receptor antagonist,was microinjected into the TMn and recorded sleep-wakefulness states for 24 h.Results(1) The ratio during 24 h of wakefulness(W),light slow wave sleep(SWS1) were respectively

关键词： gabaergic neurons GABAA-receptor antagonist histaminergic neuron neurotoxic lesion tuberomammillary nucles ventrolateral preoptic area