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Whole-brain mapping of monosynaptic afferents to GABAergic neurons in the sublaterodorsal tegmental nucleus of mice 认领 引用
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作者 Zhi-Gang Zhong Shang-Qi Tang +5 位作者 Hui Ben Jia-Lin Yang Yong-Hua Chen Wei-Min Qu Zhi-Li Huang Mei-Hong Qiu 《Zoological Research》 SCIE CAS CSCD 2025年第6期1501-1515,共15页
The sublaterodorsal tegmental nucleus(SLD) is a critical hub for regulating rapid eye movement(REM) sleep and muscle atonia,with its dysfunction linked to various disorders such as REM sleep behavior disorder(RBD) and... The sublaterodorsal tegmental nucleus(SLD) is a critical hub for regulating rapid eye movement(REM) sleep and muscle atonia,with its dysfunction linked to various disorders such as REM sleep behavior disorder(RBD) and cataplexy.Despite its physiological significance,the presynaptic patterns influencing SLD γ-aminobutyric acid(GABA)ergic neurons—one of the primary neuronal subtypes within the SLD—remain poorly understood.This study applied a modified rabies virus tracing system combined with a Cre/lox P-based genetic approach to map and quantify the whole-brain monosynaptic afferents to SLD GABAergic neurons in mice.In total,139 anatomically distinct nuclei were identified as sources of direct input,with predominant projections originating from the midbrain,pons,and medulla.Ipsilateral contributions accounted for67.99% of all traced inputs,while 32.01% were contralateral.Prominent sources included the mesencephalic reticular nucleus,superior colliculus,oral part of the pontine reticular nucleus,gigantocellular reticular nucleus,lateral hypothalamic area,and zona incerta neurons.Several nuclei displayed contralateral projection biases.Immunofluorescence staining revealed molecular diversity among input neurons,suggesting that SLD GABAergic neurons integrate signals from anatomically and functionally distinct neuronal populations.These findings provide a comprehensive anatomical framework for understanding how SLD GABAergic neurons integrate multisource inputs and offer new perspectives for investigating their involvement in regulating complex physiological functions,including sleep and motor control. 展开更多
关键词 Sublaterodorsal tegmental nucleus GABAergic neurons Monosynaptic inputs RBD Cataplexy
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Dopaminergic Neurons in the Ventral Tegmental–Prelimbic Pathway Promote the Emergence of Rats from Sevoflurane Anesthesia 认领 引用 被引量：14
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作者 Yanping Song Ruitong Chu +6 位作者 Fuyang Cao Yanfeng Wang Yanhong Liu Jiangbei Cao Yongxin Guo Weidong Mi Li Tong 《Neuroscience Bulletin》 SCIE CAS CSCD 2022年第4期417-428,共12页
Dopaminergic neurons in the ventral tegmental area(VTA)play an important role in cognition,emergence from anesthesia,reward,and aversion,and their projection to the cortex is a crucial part of the"bottom-up"... Dopaminergic neurons in the ventral tegmental area(VTA)play an important role in cognition,emergence from anesthesia,reward,and aversion,and their projection to the cortex is a crucial part of the"bottom-up"ascending activating system.The prelimbic cortex(PrL)is one of the important projection regions of the VTA.However,the roles of dopaminergic neurons in the VTA and the VTADA–PrL pathway under sevoflurane anesthesia in rats remain unclear.In this study,we found that intraperitoneal injection and local microinjection of a dopamine D1 receptor agonist(Chloro-APB)into the PrL had an emergence-promoting effect on sevoflurane anesthesia in rats,while injection of a dopamine D1 receptor antagonist(SCH23390)deepened anesthesia.The results of chemogenetics combined with microinjection and optogenetics showed that activating the VTADA–PrL pathway prolonged the induction time and shortened the emergence time of anesthesia.These results demonstrate that the dopaminergic system in the VTA has an emergence-promoting effect and that the bottom-up VTADA–PrL pathway facilitates emergence from sevoflurane anesthesia. 展开更多
关键词 Ventral tegmental area Prelimbic cortex Dopamine Sevoflurane General anesthesia
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Laterodorsal Tegmentum and Pedunculopontine Tegmental Nucleus Circuits Regulate Renal Functions: Neuroanatomical Evidence in Mice Models 认领 引用 被引量：5
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作者 叶达伟 郭晴晴 +7 位作者 冯觉平 刘成 杨辉 高峰 周外平 周伶 项红兵 李荣春 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 2012年第2期216-220,共5页
Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers p... Neurons in the laterodorsal tegmentum (LDTg) and pedunculopontine tegmental nucleus (PPTg) play important roles in central autonomic circuits of the kidney. In this study, we used a combination of retrograde tracers pseudorabies virus (PRV)-614 and fluorescence immunohistochemistry to characterize the neuroanatomic substrate of PPTg and LDTg innervating the kidney in the mouse. PRV-614-infected neurons were retrogradely labeled in the rostral and middle parts of LDTg, and the middle and caudal parts of PPTg after tracer injection in the kidney. PRV-614/TPH double-labeled neurons were mainly localized in the rostral of LDTg, whereas PRV-614/TH neurons were scattered within the three parts of LDTg. PRV-614/TPH and PRV-614/TH neurons were located predominantly in the caudal of PPTg (cPPTg). These data provided direct neuroanatomical foundation for the identification of serotonergic and catecholaminergic projections from the mid-brain tegmentum to the kidney. 展开更多
关键词 kidney laterodorsal tegmentum nucleus pedunculopontine tegmental nucleus al-pha-herpes virus tryptophan hydroxylase (TPH) tyrosine hydroxylase (TH)
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Effect of crocin carotenoid on BDNF and CREB gene expression in brain ventral tegmental area of morphine treated rats 认领 引用 被引量：6
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作者 Marzieh Rezai Mehdi Mahmoodi +3 位作者 Ayat Kaeidi Mojgan Noroozi Karimabad Alireza Khoshdel Mohammad Reza Hajizadeh 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2018年第8期387-393,共7页
Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area(VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In... Objective: To investigate the effect of crocin carotenoid on BNDF and CREB gene expression in the brain ventral tegmental area(VTA) and the serum level of BDNF in morphine-treated rats compared to control. Methods: In this study, 40 male Wistar rats(200-250 g) were used in 5 experimental groups: 1) non morphine treat rats(control); 2) non morphine-treated rats with 25 mg/kg crocin carotenoid(i.p., for 21 d); 3) morphine treated rats(10 mg/kg twice a day, s.c., 21 d); 4 and 5) morphine-treated rats with 12.5 and 25 mg/kg crocin carotenoid, respectively. By the end of research, BDNF and CREB expression was determined by real-time-PCR method. ELISA analysis was also applied for assessing the serum BDNF level. Results: The data indicated that morphine treatment could cause a significant decrease in BDNF and CREB gene expression(P<0.01 and P<0.001, respectively) in brain VTA as well as serum level of BDNF(P<0.01) in comparison to control group. Treatment with 25 mg/kg crocin carotenoid caused a significant enhancement in BDNF and CREF gene expression(P<0.01 and P<0.05, respectively) and serum level of BDNF(P<0.01) in morphine-treated rats in comparison to morphine-treated group. Conclusions: Regarding to obtained results, crocin carotenoid can inhibit unfavorable effects of morphine on the neural system to some extent through enhancing BDNF and CREB gene expression in brain VTA and serum level of BDNF. 展开更多
关键词 Morphine BDNF CREB Crocin Ventral tegmental area Rat
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Nicotine-induced transcriptional changes and mitochondrial dysfunction in the ventral tegmental area revealed by single-nucleus transcriptomics 认领 引用
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作者 Lei Fan Boxin Liu +8 位作者 Ru Yao Xia Gao Hongjuan Wang Sanjie Jiang Xiaomin Zheng Huan Chen Hongwei Hou Yong Liu Qingyuan Hu 《Journal of Genetics and Genomics》 SCIE CAS CSCD 2024年第11期1237-1251,共15页
Nicotine is widely recognized as the primary contributor to tobacco dependence.Previous studies have indicated that molecular and behavioral responses to nicotine are primarily mediated by ventral tegmental area(VTA)n... Nicotine is widely recognized as the primary contributor to tobacco dependence.Previous studies have indicated that molecular and behavioral responses to nicotine are primarily mediated by ventral tegmental area(VTA)neurons,and accumulating evidence suggests that glia play prominent roles in nicotine addiction.However,VTA neurons and glia have yet to be characterized at the transcriptional level during the progression of nicotine self-administration.Here,a male mouse model of nicotine self-administration is established and the timing of three critical phases(pre-addiction,addicting,and post-addiction phase)is characterized.Single-nucleus RNA sequencing in the VTA at each phase is performed to comprehensively classify specific cell subtypes.Adaptive changes occurred during the addicting and post-addiction phases,with the addicting phase displaying highly dynamic neuroplasticity that profoundly impacts the transcription in each cell subtype.Furthermore,significant transcriptional changes in energy metabolism-related genes are observed,accompanied by notable structural alterations in neuronal mitochondria during the progression of nicotine self-administration.The results provide insights into mechanisms underlying the progression of nicotine addiction,serving as an important resource for identifying potential molecular targets for nicotine cessation. 展开更多
关键词 Single-nucleus transcriptomics Ventral tegmental area Nicotine addiction Cell-type-specific alteration Mitochondrial dysfunction
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Chemogenetic activation of sublaterodorsal tegmental glutamatergic neurons alleviates rapid eye movement sleep behavior disorder symptoms in a chronic rat model of Parkinson disease 认领 引用
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作者 DU Li-da XU Lin-hao +3 位作者 LIANg Tuo Yun-Kwok WING KE Ya Wing-Ho YUNG 《中国药理学与毒理学杂志》 CAS CSCD 北大核心 2016年第10期1031-1031,共1页
Rapid eye movement(REM)sleep behavior disorder(RBD)is a parasomnia that is featured by elevated motor behaviors and dream enactments during REM sleep.Clinical observations show that RBD bears significant relevance wit... Rapid eye movement(REM)sleep behavior disorder(RBD)is a parasomnia that is featured by elevated motor behaviors and dream enactments during REM sleep.Clinical observations show that RBD bears significant relevance with several synucleinopathies such as Lewy body dementia and Parkinson disease(PD),and often develops prior to their diagnosis.Being a potential biomarker of PD,investigating the relationship of RBD symptoms and their emergence in developing PD would provide insight intoits pathogenesis.Here,in a chronic model of PD,rats with daily rotenone treatment exhibited key RBD features,including elevated sleep muscle tone,sleep fragmentation and EEG slowing at different time points.Based on detectedearly alpha synuclein aggregation and neural apoptosis in the sublaterodorsal tegmental nucleus(SLD),an area known to promote REM sleep and maintain sleep muscle atonia,the possible involvement of SLD glutamatergic neurons was interrogated.Via chemogenetic activation of SLD glutamatergic neurons,key RBD symptoms and EEG slowing in REM sleep were alleviated.These results are consistent with a progressive degeneration in REM sleep promoting pathways.Our findings provide a foundation for further studies into RBD and its relationship to neurodegenerative diseases. 展开更多
关键词 sublaterodorsal tegmental glutamatergic neurons rapid eye movement sleep behavior disorder
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Microinjection of Ghrelin into the Ventral Tegmental Area Potentiates Cocaine-Induced Conditioned Place Preference 认领 引用 被引量：2
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作者 Lindsey M. Schuette Christopher C. Gray Paul J. Currie 《Journal of Behavioral and Brain Science》 2013年第8期576-580,共5页
Prior work has shown that systemic cocaine pretreatment augments cocaine conditioned place preference (CPP) in rats. In contrast, ghrelin receptor antagonism attenuates cocaine and amphetamine-induced CPP. In order to... Prior work has shown that systemic cocaine pretreatment augments cocaine conditioned place preference (CPP) in rats. In contrast, ghrelin receptor antagonism attenuates cocaine and amphetamine-induced CPP. In order to further investigate ghrelin’s role in dopamine-mediated reward, the present report examined whether pretreament with ghrelin, administered directly into the ventral tegmental area (VTA) of the midbrain, would potentiate the rewarding properties of cocaine as measured by CPP. Adult male Sprague-Dawley rats were given access to either side of the CPP chamber in order to determine initial side preferences. The rats were then restricted to either their non-preferred or preferred side over the course of conditioning which lasted for a total of 16 consecutive days. This was followed by a final test day to then reassess preference. On days where rats were confined to their non-preferred side, ghrelin (30-300 pmol) and cocaine (0.625-10 mg/kg IP) were administered immediately prior to the conditioning trial. On alternate days rats were treated with vehicle and placed into what was initially determined to be their preferred side. CPP was calculated as the difference in percentage of total time spent in the treatment-paired compartment during the post-conditioning session and the pre-conditioning session. Our results indicated that both cocaine and ghrelin elicited CPP and that ghrelin pretreatment potentiated the effect of cocaine on place preference. Overall, these findings provide additional support for the argument that ghrelin signaling within the VTA enhances the rewarding effects of psychostimulant compounds. 展开更多
关键词 Cocaine Conditioned Place Preference Ghrelin Psychostimulant Midbrain Ventral Tegmental Area
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Ventral Tegmental Area Neuronal Activity Correlates to Animals’ Behavioral Response to Chronic Methylphenidate Recorded from Adolescent SD Male Rats 认领 引用
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作者 Zachary Jones Cruz Reyes Vazquez Nachum Dafny 《Journal of Behavioral and Brain Science》 2014年第4期168-189,共22页
Methylphenidate (MPD) is considered as the first-line pharmacotherapy to treat ADHD. More recently, MPD has also been used as a cognitive enhancement recreationally. Its therapeutic effects are not fully understood, n... Methylphenidate (MPD) is considered as the first-line pharmacotherapy to treat ADHD. More recently, MPD has also been used as a cognitive enhancement recreationally. Its therapeutic effects are not fully understood, nor are the long term effects of the drug on brain development. The ventral tegmental area (VTA) neuronal activity was recorded from freely behaving adolescent rats using a wireless recording system. Five groups were used: saline, 0.6, 2.5, 5.0 and 10.0 mg/kg MPD. The experiment lasted for 10 days. This study demonstrated that VTA neurons respond to MPD in a dose response characteristic and the same dose of MPD can cause both behavioral sensitization and behavioral tolerance. The neuronal unit activity was evaluated based on the animals’ behavioral activity following chronic MPD administration. The study showed that the animals’ behavioral response to different acute MPD of 0.6, 2.5 and 10.0 mg/kg doses responded in a dose response characteristics. Moreover, the same chronic dose of 0.6, 2.5, and 10.0 mg/kg MPD elicits in some animals’ behavioral sensitization and in some others behavioral tolerance. Therefore, the neuronal activity recorded from animals expressing behavioral sensitization was analyzed separately from the neuronal activity recorded from of behaviorally tolerant animals and it was found that the VTA units of the behaviorally sensitization animals responded significantly different to the drug than those VTA units recorded from animals expressing behavioral tolerance. 展开更多
关键词 Ritalin Electrophysiology Neuronal Activity Behavior Ventral Tegmental Area
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Local infusion of low, but not high, doses of alcohol into the anterior ventral tegmental area causes release of accumbal dopamine 认领 引用
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作者 Elisabet Jerlhag Jorgen A. Engel 《Open Journal of Psychiatry》 2014年第1期53-59,共7页
The mesolimbic dopamine system consisting of dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens (N.Acc.) mediates the reinforcing effects of addictive drugs including alcoho... The mesolimbic dopamine system consisting of dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens (N.Acc.) mediates the reinforcing effects of addictive drugs including alcohol. Given that VTA is a heterogeneous area and that alcohol, in rather low doses, interacts directly with ligand-gated ion channels, we hypothesised that low, rather than high, doses of alcohol into the VTA activate the mesolimbic dopamine system and that alcohol may have different effects in the anterior and posterior parts of the VTA. The present study was undertaken to investigate this hypothesis. The present series of experiment show that infusion of a low dose of alcohol (20 mM) into the anterior, but not posterior, part of the VTA increases accumbal dopamine release in rats. In addition, higher doses of alcohol (100 or 300 mM) into the anterior or posterior part of the VTA do not affect the release of dopamine in the N.Acc., suggesting that low doses of alcohol can activate the mesolimbic dopamine system via mechanisms in the VTA. These data contribute to understanding the neuronal mechanisms underlying the dependence-producing properties of alcohol and could tentatively contribute to that new treatment strategies for alcohol use disorder can be developed. 展开更多
关键词 Alcohol Ventral Tegmental Area Nucleus Accumbens Dopamine Rats
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Targeting the dopaminergic midbrain in Alzheimer's disease:Therapeutic potential of focusing on specific neural circuits rather than single molecular pathways 认领 引用
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作者 Emanuele Claudio Latagliata Stefano Puglisi-Allegra Marcello D'Amelio 《Neural Regeneration Research》 SCIE CAS CSCD 2026年第9期4251-4252,共2页
Alzheimer's disease(AD) remains one of the most unyielding challenges in neurology.Its complexity and heterogeneity underscore a critical need to explo re additional mechanisms that can be targeted in the early st... Alzheimer's disease(AD) remains one of the most unyielding challenges in neurology.Its complexity and heterogeneity underscore a critical need to explo re additional mechanisms that can be targeted in the early stages of the disease to prevent the worsening of functional decline.Converging basic-science and emerging clinical evidence now implicates progressive degeneration of the mesocorticolimbic dopamine(DA) system,particularly neurons in the ventral tegmental area(VTA),as a newly recognized event that predicts the onset of memory loss and occurs well before amyloid-β(Aβ) plaque deposition(Sala et al.,2021),as demonstrated in the Tg2576 mouse model of AD(Nobili et al.,2017;Cordella et al.,2018;La Barbera et al.,2022;Spoleti et al.,2024). 展开更多
关键词 tg mouse model progressive degeneration ventral tegmental area amyloid plaque deposition memory loss alzheimers disease ad mesocorticolimbic dopamine system neurology
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Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain 认领 引用 被引量：7
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作者 Chun-Kui Zhang Pan Wang +16 位作者 Yuan-Yuan Ji Jian-Shuai Zhao Jun-Xiang Gu Xian-Xia Yan Hong-Wei Fan Ming-Ming Zhang Yu Qiao Xiao-Die Liu Bao-Juan Li Ming-Hui Wang Hai-Long Dong Hao-Hong Li Peng-Cheng Huang Yun-Qing Li Wu-Gang Hou Jin-Lian Li Tao Chen 《Science China(Life Sciences)》 SCIE CAS CSCD 2024年第1期67-82,共16页
Chronic pain often develops severe mood changes such as depression.However,how chronic pain leads to depression remains elusive and the mechanisms determining individuals’responses to depression are largely unexplore... Chronic pain often develops severe mood changes such as depression.However,how chronic pain leads to depression remains elusive and the mechanisms determining individuals’responses to depression are largely unexplored.Here we found that depression-like behaviors could only be observed in 67.9%of mice with chronic neuropathic pain,leaving 32.1%of mice with depression resilience.We determined that the spike discharges of the ventral tegmental area(VTA)-projecting lateral habenula(LHb)glutamatergic(Glu)neurons were sequentially increased in sham,resilient and susceptible mice,which consequently inhibited VTA dopaminergic(DA)neurons through a LHbGlu-VTAGABA-VTADA circuit.Furthermore,the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic manner.Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain.Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation. 展开更多
关键词 chronic pain depression lateral habenula ventral tegmental area dopamine susceptibility
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Brain region-specific roles of brain-derived neurotrophic factor in social stress-induced depressive-like behavior 认领 引用 被引量：7
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作者 Man Han Deyang Zeng +7 位作者 Wei Tan Xingxing Chen Shuyuan Bai Qiong Wu Yushan Chen Zhen Wei Yufei Mei Yan Zeng 《Neural Regeneration Research》 SCIE CAS CSCD 2025年第1期159-173,共15页
Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice ... Brain-derived neurotrophic factor is a key factor in stress adaptation and avoidance of a social stress behavioral response.Recent studies have shown that brain-derived neurotrophic factor expression in stressed mice is brain region–specific,particularly involving the corticolimbic system,including the ventral tegmental area,nucleus accumbens,prefrontal cortex,amygdala,and hippocampus.Determining how brain-derived neurotrophic factor participates in stress processing in different brain regions will deepen our understanding of social stress psychopathology.In this review,we discuss the expression and regulation of brain-derived neurotrophic factor in stress-sensitive brain regions closely related to the pathophysiology of depression.We focused on associated molecular pathways and neural circuits,with special attention to the brain-derived neurotrophic factor–tropomyosin receptor kinase B signaling pathway and the ventral tegmental area–nucleus accumbens dopamine circuit.We determined that stress-induced alterations in brain-derived neurotrophic factor levels are likely related to the nature,severity,and duration of stress,especially in the above-mentioned brain regions of the corticolimbic system.Therefore,BDNF might be a biological indicator regulating stress-related processes in various brain regions. 展开更多
关键词 amygdala chronic mild stress chronic social defeat stress corticolimbic system depression hippocampus medial prefrontal cortex nucleus accumbens social stress models ventral tegmental area
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Single-Nucleus RNA-Seq Reveals PTSD-Associated Transcriptional Changes in Dopaminergic Neurons of the Lateral VTA 认领 引用
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作者 Peiling Zhou Hongwei Yan +5 位作者 Jingtong Wu Qinghui Lan Xue-Min Wang Jin-Jun Ding Hai-Tao Wu Changzheng Zhang 《Neuroscience Bulletin》 SCIE CAS CSCD 2025年第10期1861-1866,共6页
Dear Editor,Post-traumatic stress disorder(PTSD)is a chronic neuropsychiatric disorder triggered by severe traumatic events,characterized by persistent intrusive memories,emotional dysregulation,hyperarousal,and avoid... Dear Editor,Post-traumatic stress disorder(PTSD)is a chronic neuropsychiatric disorder triggered by severe traumatic events,characterized by persistent intrusive memories,emotional dysregulation,hyperarousal,and avoidance behaviors[1,2].PTSD is associated with significant gene expression changes in key brain regions,including the ventral tegmental area(VTA),which may underlie dysregulation of dopaminergic signaling and stress-related behaviors[3]. 展开更多
关键词 PTSD lateral VTA chronic neuropsychiatric disorder gene expression changes ventral tegmental dopaminergic neurons traumatic events transcriptional changes
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Dopaminergic neurons in the dorsal raphe nucleus may modulate social dominance in mice 认领 引用
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作者 Ying-Juan Liu Qin An +8 位作者 Bai-Lin Song Jia Tian Lu Ren Ya-Han Sun Jiao-Wen Wu Jie Zhou Zhi-Xiong He Fa-Dao Tai Lai-Fu Li 《Zoological Research》 SCIE CAS CSCD 2025年第5期996-1008,共13页
Social hierarchies are central to the organizational structure of group-living species,shaping individual physiology,behavior,and social interactions.Dopaminergic(DA)systems,particularly within the ventral tegmental a... Social hierarchies are central to the organizational structure of group-living species,shaping individual physiology,behavior,and social interactions.Dopaminergic(DA)systems,particularly within the ventral tegmental area(VTA)and dorsal raphe nucleus(DR),have been linked to motivation and competitive behaviors,yet their region-specific contributions to social dominance remain insufficiently defined.This study investigated the role of VTA and DR DA neurons in regulating social dominance in sexually naïve male C57BL/6J mice.Stable hierarchies were established using the tube test,after which both dominant and subordinate mice exhibited elevated c-Fos expression within the VTA and DR.Notably,dominant mice displayed significantly greater c-Fos activation in DR DA neurons compared to subordinates.Fiber photometry revealed that DA neurons in both regions were activated during proactive push behaviors and inhibited during passive retreats,with DR neurons showing stronger activation during dominance-related actions.Chemogenetic inhibition of DR DA neurons in dominant mice reduced their social rank,whereas activation in subordinates elevated their rank.In contrast,chemogenetic modulation of VTA DA neurons had no significant effect on social dominance.Manipulation of DA neurons in both regions produced rank-dependent changes in specific anxiety-like behavioral phenotypes.These findings highlight the distinct roles of DR and VTA DA neurons in social hierarchy regulation,identifying DR DA neurons as a critical component in the modulation of social dominance. 展开更多
关键词 Social hierarchy Dorsal raphe nucleus Ventral tegmental area Dopamine Chemogenetics
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Upregulation of NR2A in Glutamatergic VTA Neurons Contributes to Chronic Visceral Pain in Male Mice 认领 引用 被引量：1
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作者 Meng-Ge Li Shu-Ting Qu +5 位作者 Yang Yu Zhenhua Xu Fu-Chao Zhang Yong-Chang Li Rong Gao Guang-Yin Xu 《Neuroscience Bulletin》 SCIE CAS CSCD 2025年第12期2113-2126,共14页
Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways.Increasing evidence suggests that imbalances in c... Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways.Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain,but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored.In the present study,the ventral tegmental area(VTA)was shown to mediate visceral pain in mice.Visceral pain stimulation increased c-Fos expression and Ca2+activity of glutamatergic VTA neurons,and optogenetic modulation of glutamatergic VTA neurons altered visceral pain.In particular,the upregulation of NMDA receptor 2A(NR2A)subunits within the VTA resulted in visceral pain in mice.Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain.Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A.In summary,our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain.These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain. 展开更多
关键词 Irritable bowel syndrome Chronic visceral pain Ventral tegmental area Glutamatergic neurons NMDA receptor 2A subunit
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KCNQ Channels in the Mesolimbic Reward Circuit Regulate Nociception in Chronic Pain in Mice 认领 引用 被引量：11
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作者 Hao-Ran Wang Su-Wan Hu +9 位作者 Song Zhang Yu Song Xiao-Yi Wang Lei Wang Yang-Yang Li Yu-Mei Yu He Liu Di Liu Hai-Lei Ding Jun-Li Cao 《Neuroscience Bulletin》 SCIE CAS CSCD 2021年第5期597-610,共14页
Mesocorticolimbic dopaminergic(DA) neurons have been implicated in regulating nociception in chronic pain, yet the mechanisms are barely understood. Here, we found that chronic constructive injury(CCI) in mice increas... Mesocorticolimbic dopaminergic(DA) neurons have been implicated in regulating nociception in chronic pain, yet the mechanisms are barely understood. Here, we found that chronic constructive injury(CCI) in mice increased the firing activity and decreased the KCNQ channel-mediated M-currents in ventral tegmental area(VTA) DA neurons projecting to the nucleus accumbens(NAc). Chemogenetic inhibition of the VTA-to-NAc DA neurons alleviated CCI-induced thermal nociception.Opposite changes in the firing activity and M-currents were recorded in VTA DA neurons projecting to the medial prefrontal cortex(mPFC) but did not affect nociception. In addition, intra-VTA injection of retigabine, a KCNQ opener, while reversing the changes of the VTA-to-NAc DA neurons, alleviated CCI-induced nociception, and this was abolished by injecting exogenous BDNF into the NAc.Taken together, these findings highlight a vital role of KCNQ channel-mediated modulation of mesolimbic DA activity in regulating thermal nociception in the chronic pain state. 展开更多
关键词 Nociception Mesocorticolimbic system Ventral tegmental area Brain-derived neurotrophic factor KCNQ Retigabine Chronic neuropathic pain
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An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in 认领 引用 被引量：4
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作者 Ting-Ting Zhang Su-Shan Guo +7 位作者 Hui-Ying Wang Qi Jing Xin Yi Zi-Han Hu Xin-Ren Yu Tian-Le Xu Ming-Gang Liu Xuan Zhao 《Neuroscience Bulletin》 SCIE CAS CSCD 2023年第5期793-807,共15页
Itch is an unpleasant sensation that provokes the desire to scratch.While acute itch serves as a protec-tive system to warn the body of external irritating agents,chronic itch is a debilitating but poorly-treated clin... Itch is an unpleasant sensation that provokes the desire to scratch.While acute itch serves as a protec-tive system to warn the body of external irritating agents,chronic itch is a debilitating but poorly-treated clinical dis-ease leading to repetitive scratching and skin lesions.How-ever,the neural mechanisms underlying the pathophysiol-ogy of chronic itch remain mysterious.Here,we identified a cell type-dependent role of the anterior cingulate cortex(ACC)in controlling chronic itch-related excessive scratch-ing behaviors in mice.Moreover,we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area(VTA)that was critically involved in chronic itch.Furthermore,we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch.Finally,the ACC neurons were shown to predomi-nantly innervate the non-dopaminergic neurons of the VTA.Taken together,our findings uncover a cortex-midbrain cir-cuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention. 展开更多
关键词 sAnterior cingulate cortex Chronic itch Ventral tegmental area-Chemogenetics Neural circuit
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R-apomorphine protects against 6-hydroxydopamine-induced nigrostriatal damage in rat 认领 引用 被引量：2
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作者 袁红 梁立武 +5 位作者 郑静晨 吉慧如 王梅康 张海英 曹力 许建阳 《Neuroscience Bulletin》 CAS 2006年第6期331-338,共8页
Objective The aim of the present study was not only to assess the retrograde degenerative changes in the dopaminergic neurons of the substantia nigra （SN） and ventral tegmental area （VTA） after injection of 6-hydr... Objective The aim of the present study was not only to assess the retrograde degenerative changes in the dopaminergic neurons of the substantia nigra （SN） and ventral tegmental area （VTA） after injection of 6-hydroxydopamine （6-OHDA） into the striatum, but also to use this 6-OHDA model of Parkinson＇s disease to explore the possible neuroprotective effect of R-apomorphine （R-APt）. Methods The partial lesion was obtained by intrastriatal administration of 6-OHDA. R- APt administration （10 mg/kg, s.c.） started 15 min prior to lesioning and continued daily for another 22 days post surgery. Testing was carried out 5 weeks after lesioning. We investigated the histology and associated behavior and neurochemical changes. Structural and functional deficits were quantified by tyrosine hydroxylase （TH） / Nissl-staining cell number counting, striatal dopamine （DA） content determination and amphetamine-induced rotation analysis. Results R-APt- treatment attenuated the amphetamine-induced ipsiversive rotation 5 weeks after the lesion induction. R-APt administra- tion for 22 days significantly reduced the size of the lesion at the level of the SN from 50% （control group） to 69%. Moreover, the cell shape resembled that observed in the intact animals. R-APt treatment significantly increased the number of cells in both the lesion and the intact sides of VTA by 60%, suggesting selective neurotrophic effect of R-APt in this area. Finally, R-APt-treatment significantly attenuated the 6-OHDA-induced striatal DA depletion and normalized dihydroxyphenylacetic acid （DOPAC）/DA ratios. Conclusion We conclude that R-APt has neuroprotective and pos- sible neurotrophic effect on a striatal lesion with 6-OHDA, suggesting that this drug may have rescuing properties in patients with early stage Parkinson＇s disease. These effects are more pronounced in VTA and enhance with duration of treatment. 展开更多
关键词 R-apomorphine neuroprotection neurotrophic effect ventral tegmental area Parkinson＇s disease
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Effects of acupuncture stimulation of the sacral region on EEG and urinary bladder activity in rats 认领 引用 被引量：3
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作者 王慧 Yoshi masa Koyama Yukihiko Kayama 《World Journal of Acupuncture-Moxibustion》 CAS 2009年第1期35-40,62,共6页
Objective To observe the effect of acupuncture stimulation of the sacral segment on the excitability of the cerebral cortex and the activity of the urinary bladder and the involvement of the cholinergic neurons in the... Objective To observe the effect of acupuncture stimulation of the sacral segment on the excitability of the cerebral cortex and the activity of the urinary bladder and the involvement of the cholinergic neurons in the laterodorsal tegmental （LDT） nucleus of the brainstem in acupuncture-induced electroencephalogram （EEG） changes. Methods A total of 109 SD rats were used in the present study. Under anesthesia （urethane）, a pair of stainless steel electrodes was separately implanted into the frontal and parietal bony sutures to record EEG. Glass microelectrodes were used to record extracellular discharges of single neuron of the LDT nucleus in the brainstem. Urinary bladder pressure was recorded through a catheter inserted in the bladder and the contraction was induced by infusion of normal saline. A filiform acupuncture needle was inserted into the sacral segment Ecorresponding to Zhongliao （中髎BL 33）] and rotated manually for 1 min. Results In 27 rats whose bladder was full of normal saline, acupuncture stimulation of the sacral region suppressed the contraction activity of the bladder, the fast EEG with lower amplitude and higher frequency tuned into slow EEG with higher amplitude and lower frequency in 6 cases （22.2%）. The inhibitory effect occurred from 45 s to 12 min after acupuncture manipulation. In 82 rats whose bladder was empty, acupuncture stimulation caused the fast EEG to turn into slow EEG in 71 cases （86.6%）. Simultaneously, LDT cholinergic neurons reduced their firing rates from （2.9±1.5） Hz to （1.2±0.6） Hz （n = 12, P〈0.05）, and the reduction of LDT neuronal discharge was earlier in time than the change of EEG. Conclusion Acupuncture stimulation of the sacral region can lower the excitability of the cerebral cortex and suppress bladder activity, which is closely associated with its resultant inhibitory effect on the electrical activity of LDT cholinergic neurons. 展开更多
关键词 Acupuncture Sacral part Electroencephalogram Urinary bladder contraction Laterodorsal tegmental nucleus Cholinergic neuronal discharge
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Brain regional changes of guanine nucleotide binding protein-inhabitant 2 in acute and chronic morphine-tolerant and-dependent rats 认领 引用
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作者 Qinghua Wu Qiang Fu +3 位作者 Xinhua Wang Jianhua Zhao Liwei Liu Shirong Tang 《Neural Regeneration Research》 SCIE CAS 2008年第7期751-755,共5页
BACKGROUND： Drug addiction involves two main central nervous systems, namely the dopamine and noradrenaline systems. These systems are primarily distributed in five brain regions： the ventral tegmental area, the nuc... BACKGROUND： Drug addiction involves two main central nervous systems, namely the dopamine and noradrenaline systems. These systems are primarily distributed in five brain regions： the ventral tegmental area, the nucleus accumbens, the prefrontal cortex, the hippocampus, and the locus coeruleus. OBJECTIVE： To investigate regional changes of guanine nucleotide binding protein-inhabitant 2 （Gi2） in dopaminergic and noradrenergic neurons in brains of morphine-tolerant and -dependent rats. DESIGN, TIME, AND SETTING： A randomized control study was performed at the Department of Neurobiology in the Second Military Medical University of Chinese PLA （Shanghai, China） between September 2002 and March 2004. MATERIALS： Thirty-six, healthy, male, Sprague-Dawley （SD） rats were used to establish morphine-dependent models. Morphine hydrochloride was a product of Shenyang First Pharmaceutical Factory （China）; naloxone hydrochloride was a product of Beijing Four-Ring Pharmaceutical Factory （China）; and α subunit of Gi2 antibody was offered by Santa Cruz Biotechnology, lnc （USA）. METHODS： Thirty-six SD rats were randomly divided into six groups （n = 6）： （1） acute morphine-dependent group, （2） acute abstinent group, （3） acute control group, （4） chronic morphine-dependent group, （5） chronic abstinent group, and （6） chronic control group. Rats in the acute morphine-dependent and the acute groups were injected with morphine （5 mg/kg）, one injection every two hours, for a total of eight injections. In the acute and chronic morphine-dependent rat models, morphine withdrawal syndrome was precipitated by an injection of naloxone （5 mg/kg）. Rats in the acute control group were given a peritoneal injection of physiological saline at the same administration time as the above two groups. Rats in the chronic morphine-dependent and chronic abstinent groups were injected with morphine three times per day. The administration dose on day 1 was initially 5 mg/kg at 20：00, which increased by 5 mg/kg at 8：00, 12：00, and 20：00 until day 7. On day 13, the dose continuously increased by 10 mg/kg until a chronic morphine-dependent rat model was successfully induced. Afterwards, the rats presented with withdrawal syndromes on naloxone （5 mg/kg） at 8：00 on the same day. Rats in the chronic control group were injected with physiological saline at the same time of the two chronic groups. MAIN OUTCOME MEASURES： The concentration of Gi2 protein in the five brain regions （ventral tegmental area, nucleus accumbens, prefrontal cortex, locus coeruleus, and hippocampus） was detected by immunohistochemistry. RESULTS： In the acute morphine-dependent and acute abstinent groups, Gi2 protein concentration was significantly decreased in the nucleus accumbens, compared to the acute control group （P 〈 0.01）, while no obvious changes were detected in other brain regions. In the chronic morphine-dependent and chronic abstinent groups, Gi2 protein concentration was significantly decreased in the nucleus accumbens, but significantly increased in the locus coeruleus （P 〈 0.01 ） compared to the chronic control group. CONCLUSION： Morphine dependence and tolerance may induce obvious reductions of Gi2 protein levels in the nucleus accumbens of rats. Chronic morphine dependence desensitizes the homologous neurons. 展开更多
关键词 morphine dependenceolerance guanine nucleotide binding protein-inhabitant 2 hippocampus ventral tegmental area mucleus accumbens prefrontal cortex locus coeruleus
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