The nucleus accumbens shell(NAcSh) plays an important role in reward and aversion. Traditionally, NAc dopamine receptor 2-expressing(D2) neurons are assumed to function in aversion. However, this has been challenged b...The nucleus accumbens shell(NAcSh) plays an important role in reward and aversion. Traditionally, NAc dopamine receptor 2-expressing(D2) neurons are assumed to function in aversion. However, this has been challenged by recent reports which attribute positive motivational roles to D2 neurons. Using optogenetics and multiple behavioral tasks, we found that activation of D2 neurons in the dorsomedial NAcSh drives preference and increases the motivation for rewards, whereas activation of ventral NAcSh D2 neurons induces aversion. Stimulation of D2 neurons in the ventromedial NAcSh increases movement speed and stimulation of D2 neurons in the ventrolateral NAc Sh decreases movement speed. Combining retrograde tracing and in situ hybridization, we demonstrated that glutamatergic and GABAergic neurons in the ventral pallidum receive inputs differentially from the dorsomedial and ventral NAcSh. All together, these findings shed light on the controversy regarding the function of NAcSh D2 neurons, and provide new insights into understanding the heterogeneity of the NAcSh.展开更多
The ventral pallidum(VP) is a crucial component of the limbic loop of the basal ganglia and participates in the regulation of reward, motivation, and emotion.Although the VP receives afferent inputs from the central h...The ventral pallidum(VP) is a crucial component of the limbic loop of the basal ganglia and participates in the regulation of reward, motivation, and emotion.Although the VP receives afferent inputs from the central histaminergic system, little is known about the effect of histamine on the VP and the underlying receptor mechanism. Here, we showed that histamine, a hypothalamicderived neuromodulator, directly depolarized and excited the GABAergic VP neurons which comprise a major cell type in the VP and are responsible for encoding cues of incentive salience and reward hedonics. Both postsynaptic histamine H1 and H2 receptors were found to be expressed in the GABAergic VP neurons and co-mediate the excitatory effect of histamine. These results suggested that the central histaminergic system may actively participate in VP-mediated motivational and emotional behaviors via direct modulation of the GABAergic VP neurons. Our findings also have implications for the role of histamine and the central histaminergic system in psychiatric disorders.展开更多
Organisms must make sense of a constant stream of sensory inputs from both internal and external sources which compete for attention by determining which ones are salient.The ability to detect and respond appropriatel...Organisms must make sense of a constant stream of sensory inputs from both internal and external sources which compete for attention by determining which ones are salient.The ability to detect and respond appropriately to potentially salient stimuli in the environment is critical to all organisms.However,the neural circuits that process salience are not fully understood.Here,we identify a population of glutamatergic neurons in the ventral pallidum(VP)that play a unique role in salience processing.Using cell-type-specific fiber photometry,we find that VP glutamatergic neurons are robustly activated by a variety of aversion-and reward-related stimuli,as well as novel social and non-social stimuli.Inhibition of the VP glutamatergic neurons reduces the ability to detect salient stimuli in the environment,such as aversive cue,novel conspecific and novel object.Besides,VP glutamatergic neurons project to both the lateral habenula(LHb)and the ventral tegmental area(VTA).Together,our findings demonstrate that the VP glutamatergic neurons participate in salience processing and therefore provide a new perspective on treating several neuropsychiatric disorders,including dementia and psychosis.展开更多
目的观察单侧黑质纹状体通路损毁对大鼠腹侧苍白球(ventral pallidum,VP)神经元电活动的影响。方法采用在体细胞外记录方法研究正常大鼠和帕金森病(Parkinson s disease,PD)大鼠VP神经元放电频率和放电形式的变化。结果对照组大鼠VP神...目的观察单侧黑质纹状体通路损毁对大鼠腹侧苍白球(ventral pallidum,VP)神经元电活动的影响。方法采用在体细胞外记录方法研究正常大鼠和帕金森病(Parkinson s disease,PD)大鼠VP神经元放电频率和放电形式的变化。结果对照组大鼠VP神经元的平均放电频率为(16.1±1.2)Hz(n=41);2周和4周PD组大鼠VP神经元的平均放电频率分别是(9.3±0.8)Hz(n=43)和(8.6±1.0)Hz(n=47),与对照组相比,VP神经元的平均放电频率显著减低(P均<0.001),但两PD模型组之间VP神经元的平均放电频率无明显差异(P>0.05)。在对照组大鼠,规则放电的神经元占44%(18/41),不规则放电的神经元占52%(21/41),爆发式放电的神经元仅占4%(2/41);在2周和4周PD模型组大鼠,具有规则、不规则和爆发式放电的VP神经元的百分比分别为14%(6/43)、47%(20/43)、39%(17/43)和17%(8/47)、49%(23/47)、34%(16/47),2周和4周PD组大鼠VP中爆发式放电的神经元明显多于对照组(P均<0.01),而两PD模型组之间VP神经元的放电形式未见显著性差异(P>0.05)。结论单侧黑质纹状体通路损毁诱发大鼠VP神经元的放电频率降低,具有爆发式放电的神经元增多,这种变化可能与伏核-VP的抑制性神经传递增强有关。展开更多
Establishment of animal models of schizophrenia is critical for both understanding the mechanisms underlying this severe mental disease and developing new antipsychotics. This paper starts from the theoretical root of...Establishment of animal models of schizophrenia is critical for both understanding the mechanisms underlying this severe mental disease and developing new antipsychotics. This paper starts from the theoretical root of sensory gating, the 損rotection-of-processing?theory, then thoroughly describes the representative studies over the past decade on the mechanism underlying prepulse inhibition and on those underlying modulation of prepulse inhibition, which is the normal startle suppression caused by the weak stimulus preceding the intense startling stimulus. The main methods for inducing prepulse inhibition deficits in experimental animals include: ⅰ) modulations of neuro- transmission that are closely associated with schizophrenia; ⅱ) focal lesions or pharmacological manipulations of brain structures in the cortico-striato-pallido-pontine circuit; and ⅲ) maternal deprivation or social isolation. Six essential topics for studies in modeling schizophrenia are suggested at the last part of this review.展开更多
基金supported by National Science Foundation of China grants 31571095 and 91332122a Key Scientific Technological Innovation Research project from the Ministry of Education+1 种基金a grant from Insitute Guo Qiang at Tsinghua Universityfunding from the Beijing Program on the Study of Functional Chips and Related Core Technologies of Brain-inspired Computing Systems。
文摘The nucleus accumbens shell(NAcSh) plays an important role in reward and aversion. Traditionally, NAc dopamine receptor 2-expressing(D2) neurons are assumed to function in aversion. However, this has been challenged by recent reports which attribute positive motivational roles to D2 neurons. Using optogenetics and multiple behavioral tasks, we found that activation of D2 neurons in the dorsomedial NAcSh drives preference and increases the motivation for rewards, whereas activation of ventral NAcSh D2 neurons induces aversion. Stimulation of D2 neurons in the ventromedial NAcSh increases movement speed and stimulation of D2 neurons in the ventrolateral NAc Sh decreases movement speed. Combining retrograde tracing and in situ hybridization, we demonstrated that glutamatergic and GABAergic neurons in the ventral pallidum receive inputs differentially from the dorsomedial and ventral NAcSh. All together, these findings shed light on the controversy regarding the function of NAcSh D2 neurons, and provide new insights into understanding the heterogeneity of the NAcSh.
基金supported by the National Natural Science Foundation of China (81671107, 31330033, 91332124, 31471112, 31600834, and the NSFC and the Research Grants Council Joint Research Scheme 31461163001)the Ministry of Education of China (Fundamental Research Funds for the Central Universities 020814380071, 020814380048 and 020814380091)the China Postdoctoral Science Foundation (2017T100351)
文摘The ventral pallidum(VP) is a crucial component of the limbic loop of the basal ganglia and participates in the regulation of reward, motivation, and emotion.Although the VP receives afferent inputs from the central histaminergic system, little is known about the effect of histamine on the VP and the underlying receptor mechanism. Here, we showed that histamine, a hypothalamicderived neuromodulator, directly depolarized and excited the GABAergic VP neurons which comprise a major cell type in the VP and are responsible for encoding cues of incentive salience and reward hedonics. Both postsynaptic histamine H1 and H2 receptors were found to be expressed in the GABAergic VP neurons and co-mediate the excitatory effect of histamine. These results suggested that the central histaminergic system may actively participate in VP-mediated motivational and emotional behaviors via direct modulation of the GABAergic VP neurons. Our findings also have implications for the role of histamine and the central histaminergic system in psychiatric disorders.
基金supported by the National Natural Science Foundation of China(31922029,31671086,61890951&61890950 to J.H.and 31700909 to M.C.)partly supported by the open funds of the State Key Laboratory of Medical Neurobiology.
文摘Organisms must make sense of a constant stream of sensory inputs from both internal and external sources which compete for attention by determining which ones are salient.The ability to detect and respond appropriately to potentially salient stimuli in the environment is critical to all organisms.However,the neural circuits that process salience are not fully understood.Here,we identify a population of glutamatergic neurons in the ventral pallidum(VP)that play a unique role in salience processing.Using cell-type-specific fiber photometry,we find that VP glutamatergic neurons are robustly activated by a variety of aversion-and reward-related stimuli,as well as novel social and non-social stimuli.Inhibition of the VP glutamatergic neurons reduces the ability to detect salient stimuli in the environment,such as aversive cue,novel conspecific and novel object.Besides,VP glutamatergic neurons project to both the lateral habenula(LHb)and the ventral tegmental area(VTA).Together,our findings demonstrate that the VP glutamatergic neurons participate in salience processing and therefore provide a new perspective on treating several neuropsychiatric disorders,including dementia and psychosis.
文摘目的观察单侧黑质纹状体通路损毁对大鼠腹侧苍白球(ventral pallidum,VP)神经元电活动的影响。方法采用在体细胞外记录方法研究正常大鼠和帕金森病(Parkinson s disease,PD)大鼠VP神经元放电频率和放电形式的变化。结果对照组大鼠VP神经元的平均放电频率为(16.1±1.2)Hz(n=41);2周和4周PD组大鼠VP神经元的平均放电频率分别是(9.3±0.8)Hz(n=43)和(8.6±1.0)Hz(n=47),与对照组相比,VP神经元的平均放电频率显著减低(P均<0.001),但两PD模型组之间VP神经元的平均放电频率无明显差异(P>0.05)。在对照组大鼠,规则放电的神经元占44%(18/41),不规则放电的神经元占52%(21/41),爆发式放电的神经元仅占4%(2/41);在2周和4周PD模型组大鼠,具有规则、不规则和爆发式放电的VP神经元的百分比分别为14%(6/43)、47%(20/43)、39%(17/43)和17%(8/47)、49%(23/47)、34%(16/47),2周和4周PD组大鼠VP中爆发式放电的神经元明显多于对照组(P均<0.01),而两PD模型组之间VP神经元的放电形式未见显著性差异(P>0.05)。结论单侧黑质纹状体通路损毁诱发大鼠VP神经元的放电频率降低,具有爆发式放电的神经元增多,这种变化可能与伏核-VP的抑制性神经传递增强有关。
基金This work was supported by the National Natural Sciences Foundation of China(Grant No.30200080)the Ministry of Science and Technology of China(Grant No.2002CCA01000)the Ministry of Education of China(Grant No.02170).
文摘Establishment of animal models of schizophrenia is critical for both understanding the mechanisms underlying this severe mental disease and developing new antipsychotics. This paper starts from the theoretical root of sensory gating, the 損rotection-of-processing?theory, then thoroughly describes the representative studies over the past decade on the mechanism underlying prepulse inhibition and on those underlying modulation of prepulse inhibition, which is the normal startle suppression caused by the weak stimulus preceding the intense startling stimulus. The main methods for inducing prepulse inhibition deficits in experimental animals include: ⅰ) modulations of neuro- transmission that are closely associated with schizophrenia; ⅱ) focal lesions or pharmacological manipulations of brain structures in the cortico-striato-pallido-pontine circuit; and ⅲ) maternal deprivation or social isolation. Six essential topics for studies in modeling schizophrenia are suggested at the last part of this review.
