我国科学家得到完整的大脑(mPFC)远程投射图谱

<正>内侧前额叶皮层(mPFC)包含GABA能中间神经元群体,其在认知和情绪中起不同作用。mPFC中的GABA能神经元在调节工作记忆,决策和与动机和厌恶行为相关的情绪方面发挥重要作用,其功能障碍与各种疾病有关,包括重性抑郁症,精神分裂症和癫痫。mPFC中GABA能神经元的亚型包括表达小白蛋白(PV+),表达生长抑素(SST+)和表达血管活性肠肽     

GABA引起正常和病理性疼痛大鼠DRG神经元去极化反应的比较

为探究GABA在痛觉信息传递中的作用,观察分析了γ-氨基丁酸(GABA)在神经病理性疼痛中的作用。制备神经病理性疼痛大鼠模型,取其L4-L5背根神经节(dorsal root ganglion,DRG),运用细胞内微电极记录技术观察在灌流GABA及其受体阻断剂的情况下,引起DRG神经元膜电位的变化。结果表明,病理性疼痛模型组大鼠的DRG神经元对不同浓度GABA引起的去极化反应均明显小于正常对照组大鼠(P0.05),这说明神经病理性疼痛可通过减弱GABA介导的突触前抑制易化痛觉信息的传递。     

鸣禽鸣啭控制核团内GABA能神经元的分布研究

应用免疫组化方法对鸣禽粟鹀(Emberiza rutila)鸣啭控制核团内GABA能神经元的分布进行了研究，在高级发声中枢(HVC，high vocal center)，古纹状体粗核(RA，the robust nucleus of the archistrialum)，X区(Arca X)3个前脑核团内有GABA样免疫反应出现．HVC和RA中GABA能神经元胞体大小存在性别和季节间的差异．结果提示GABA能神经元可能参与了鸣禽鸣啭的产生和鸣啭学习。     

尼氟灭酸对CCI模型鼠DRG神经元GABA介导膜电流的影响

为观察尼氟灭酸(NFA)对坐骨神经慢性压迫损伤(CCI)所导致的神经病理性痛大鼠的背根神经节(dorsal root ganglion,DRG)神经元上GABAA受体激活电流的影响,探讨尼氟灭酸在神经病理性疼痛时在脊髓水平的作用及可能机制。采用如下方法:(1)制作CCI模型。(2)运用热板实验检测CCI组、假手术组术侧下肢热缩足反射潜伏期的变化。(3)运用全细胞膜片钳技术记录CCI模型组术侧、假手术组术侧、正常组DRG神经元上GABAA受体激活电流的幅度。(4)记录尼氟灭酸对正常组和CCI组术侧DRG神经元上GABAA受体激活电流的调节作用。结果显示,(1)CCI组术侧下肢热缩足反射潜伏期明显缩短。(2)GABA(1~1000μmol/L)可以使DRG神经元产生浓度依赖的内向电流(P0.05,n=10)。(3)CCI组1~100μmol/L GABA激活电流幅值显著小于假手术组和正常对照组(P0.01,n=6)。假手术组和正常对照组GABA电流差异无统计学意义。(4)NFA(1~100μmol/L)对正常组、CCI组的DRG神经元上GABA激活的电流均有抑制作用,该抑制作用具有浓度依赖性,且正常组的抑制作用更明显(P0.01,n=5)。由此可知,NFA对CCI模型大鼠DRG神经元GABA激活电流的抑制作用相比较正常组有所减弱,这可能是由于CCI模型的DRG神经元上钙激活氯通道的数量增加。     

组胺能与γ-氨基丁酸能神经传递在间位核神经元信息加工中的作用(英文)

小脑间位核(interpositus nucleus,IN)主要接受γ-氨基丁酸(GABA)能纤维支配,同时接受组胺能纤维的调节.本研究在小脑脑片上研究了GABA和组胺对单个IN神经元电活动的共同作用.持续灌流组胺或同时施加组胺和GABA,81.2%(69/85)神经元,GABA及其激动剂的效应都被组胺削弱(持续灌流n=33;同时施加n=36).这种削弱效应能够被组胺H2受体阻断剂ranitidine(n=10)和PKA抑制剂H-89阻断(n=8),fors-kolin模拟组胺的效应(n=9).结果表明组胺和GABA对IN神经元的电活动具有交互调节作用:通过激活H2受体偶联的G-protein-AC-PKA信号通路,磷酸化GABAB和GABAA受体,降低受体功能.推测受体间的对话的工作模式,可能是整个大脑神经元活动的某些药理作用和生理活动调节的基础;如果对话紊乱,可能导致大脑功能障碍.     

组胺能与y-氨基丁酸能神经传递在问位核神经元信息加工中的作用

小脑间位核（interpositusnucleus,IN）主要接受1一氨基丁酸（GABA）能纤维支配,同时接受组胺能纤维的调节．本研究在小脑脑片上研究了GABA和组胺对单个IN神经元电活动的共同作用．持续灌流组胺或同时施加组胺和GABA,81．2％（69／85）神经元,GABA及其激动剂的效应都被组胺削弱（持续灌流n=33;同时施加n=36）．这种削弱效应能够被纽胺H,受体阻断剂ranitidine（n=10）和PK。抑制剂H一89阻断（n=8）,fors—kolin模拟组胺的效应（n=9）．结果表明组胺和GABA对IN神经元的电活动具有交互调节作用：通过激活H：受体偶联的G—protein—AC—PK。信号通路,磷酸化GABAB和GABA^受体,降低受体功能．推测受体间的对话的工作模式,可能是整个大脑神经元活动的某些药理作用和生理活动调节的基础;如果对话紊乱,可能导致大脑功能障碍．     

P物质对GABAA受体介导电流的作用

应用全细胞膜片箝技术,在大鼠新鲜分离的背根神经节细胞上观察到:SP对GABA激活电流有调制作用。实验结果表明:多数受检的大鼠背根神经节神经元对SP(28/41,68.5％)和GABA(36/41,88.2％)敏感,100μmol/LSP和100μmol/L GABA激活内向电流的幅值分别为243.8±82.7pA(x±s,n=9)和1.76±0.48nA(x±s,n=13)。GABA与SP激活的内向电流明显不同,前者具有明显的去敏感现象。实验预加SP(0.001～1μmol/L)30s后再加GABA,则GABA激活电流的幅值明显减小,而且GABA激活电流减小的程度与预加SP的浓度呈量效依赖关系。SP主要抑制GABA激活电流的峰电流,对其稳态电流的抑制不明显。预加0.1μmol/L SP之后约4min左右,SP对GA-BA激活电流的抑制效率最大,为49.8±7.2％(x±s,n=7,P≤0.01),而预加SP 12min之后,SP才失去对GABA激活电流的抑制作用。     

多巴胺对鸣禽发声相关神经元活动的调控

鸣禽多巴胺(DA)神经元主要分布于中脑腹侧被盖区-黑质体致密部(VTA-SNc复合体)和中脑导水管周围灰质(PAG),并分别发出纤维投射至鸣唱控制核团前脑纹状X区、弓状皮质栎核(RA)和高级发声中枢(HVC).近年研究表明,中脑向鸣唱控制核团中释放的DA可以调控鸣唱控制核团中神经元的活动,进而调节鸣禽的鸣唱行为.该文对近年来,多巴胺对鸣禽发声相关神经元活动的调控研究做一综述.     

榆紫叶甲 Ambrostoma quadriim-pressum脑及咽下神经节GABA阳性神经元分布模式的构建

采用树脂石蜡(CP)组织包埋切片技术,结合免疫组化链霉菌抗生物素蛋白-过氧化物酶(SP)双染法,初步构建了榆紫叶甲脑及咽下神经节GABA阳性神经元的分布模式.结果显示,榆紫叶甲脑结构比较特殊:视叶不发达,但具内髓板;嗅叶不发达;蕈形体冠高度退化,而根叶相对发达;中央复合体结构明显;后脑经由围咽神经束与咽下神经结相连,咽下神经结非常发达.榆紫叶甲的所有髓区几乎都有GABA免疫阳性纤维分布.一侧脑半球及咽下神经节共存在约2 800个GABA阳性神经元,分布广泛,且趋向于集群分布.该研究表明榆紫叶甲的脑结构及GABA阳性神经元的分布模式与榆紫叶甲的生活习性、进化地位等密切相关.     

GABA能抑制参与弱噪声对下丘频率调谐的前掩蔽

在自由声场条件下，选用强度相当于纯音阈上5dB SPL、80ms的弱包络白噪声作为前掩蔽声，观察加入掩蔽声后神经元频率调谐的变化．对发生锐化的神经元导入荷包牡丹碱（Bicuculline，BIC），观察去GABA能抑制后前掩蔽效应的变化．结果显示：弱噪声前掩蔽使大部分神经元的频率调谐曲线（frequency tuning curve，FTC）锐化（P〈0．01），导入BIC后，弱噪声的抑制率下降．研究结果证实GABA能抑制参与了弱噪声所致的下丘神经元前掩蔽．     

Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease

Parkinson's disease is a widespread condition caused by the loss of midbrain neurons that synthesize the neurotransmitter dopamine. Cells derived from the fetal midbrain can modify the course of the disease, but they are an inadequate source of dopamine-synthesizing neurons because their ability to generate these neurons is unstable. In contrast, embryonic stem (ES) cells proliferate extensively and can generate dopamine neurons. If ES cells are to become the basis for cell therapies, we must develop methods of enriching for the cell of interest and demonstrate that these cells show functions that will assist in treating the disease. Here we show that a highly enriched population of midbrain neural stem cells can be derived from mouse ES cells. The dopamine neurons generated by these stem cells show electrophysiological and behavioural properties expected of neurons from the midbrain. Our results encourage the use of ES cells in cell-replacement therapy for Parkinson's disease.     

Neuron-type-specific signals for reward and punishment in the ventral tegmental area

Dopamine has a central role in motivation and reward. Dopaminergic neurons in the ventral tegmental area (VTA) signal the discrepancy between expected and actual rewards (that is, reward prediction error), but how they compute such signals is unknown. We recorded the activity of VTA neurons while mice associated different odour cues with appetitive and aversive outcomes. We found three types of neuron based on responses to odours and outcomes: approximately half of the neurons (type I, 52%) showed phasic excitation after reward-predicting odours and rewards in a manner consistent with reward prediction error coding; the other half of neurons showed persistent activity during the delay between odour and outcome that was modulated positively (type II, 31%) or negatively (type III, 18%) by the value of outcomes. Whereas the activity of type I neurons was sensitive to actual outcomes (that is, when the reward was delivered as expected compared to when it was unexpectedly omitted), the activity of type II and type III neurons was determined predominantly by reward-predicting odours. We 'tagged' dopaminergic and GABAergic neurons with the light-sensitive protein channelrhodopsin-2 and identified them based on their responses to optical stimulation while recording. All identified dopaminergic neurons were of type I and all GABAergic neurons were of type II. These results show that VTA GABAergic neurons signal expected reward, a key variable for dopaminergic neurons to calculate reward prediction error.     

Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson's disease

Human pluripotent stem cells (PSCs) are a promising source of cells for applications in regenerative medicine. Directed differentiation of PSCs into specialized cells such as spinal motoneurons or midbrain dopamine (DA) neurons has been achieved. However, the effective use of PSCs for cell therapy has lagged behind. Whereas mouse PSC-derived DA neurons have shown efficacy in models of Parkinson's disease, DA neurons from human PSCs generally show poor in vivo performance. There are also considerable safety concerns for PSCs related to their potential for teratoma formation or neural overgrowth. Here we present a novel floor-plate-based strategy for the derivation of human DA neurons that efficiently engraft in vivo, suggesting that past failures were due to incomplete specification rather than a specific vulnerability of the cells. Midbrain floor-plate precursors are derived from PSCs 11 days after exposure to small molecule activators of sonic hedgehog (SHH) and canonical WNT signalling. Engraftable midbrain DA neurons are obtained by day 25 and can be maintained in vitro for several months. Extensive molecular profiling, biochemical and electrophysiological data define developmental progression and confirm identity of PSC-derived midbrain DA neurons. In vivo survival and function is demonstrated in Parkinson's disease models using three host species. Long-term engraftment in 6-hydroxy-dopamine-lesioned mice and rats demonstrates robust survival of midbrain DA neurons derived from human embryonic stem (ES) cells, complete restoration of amphetamine-induced rotation behaviour and improvements in tests of forelimb use and akinesia. Finally, scalability is demonstrated by transplantation into parkinsonian monkeys. Excellent DA neuron survival, function and lack of neural overgrowth in the three animal models indicate promise for the development of cell-based therapies in Parkinson's disease.     

依托咪酯对腹外侧视前区神经元GABA能传递的抑制作用

目的:研究依托咪酯对大鼠腹外侧视前区神经元γ-氨基丁酸能传递的影响。方法:大鼠腹外侧视前区切片,全细胞膜片钳记录神经元抑制性突触后电流。结果:依托咪酯(0.1μmol/L)可逆性地降低腹外侧视前区神经元的诱发抑制性突触后电流幅度,但未能显著性改变其配对脉冲比率。依托咪酯(0.1μmol/L)作用下,自发抑制性突触后电流的频率与幅度均显著性下降,其动力学参数未受影响。结论:依托咪酯可作用于突触前及突触后γ-氨基丁酸受体而抑制对腹外侧视前区神经元的γ-氨基丁酸能传递,这一作用可能使其处于兴奋状态,进而抑制结节乳头体核的组胺能神经元,减少组胺释放而发挥麻醉镇静作用。     

Prediction of auditory spatial acuity from neural images on the owl's auditory space map

The owl can discriminate changes in the location of sound sources as small as 3 degrees and can aim its head to within 2 degrees of a source. A typical neuron in its midbrain space map has a spatial receptive field that spans 40 degrees--a width that is many times the behavioural threshold. Here we have quantitatively examined the relationship between neuronal activity and perceptual acuity in the auditory space map in the barn owl midbrain. By analysing changes in firing rate resulting from small changes of stimulus azimuth, we show that most neurons can reliably signal changes in source location that are smaller than the behavioural threshold. Each source is represented in the space map by a focus of activity in a population of neurons. Displacement of the source causes the pattern of activity in this population to change. We show that this change predicts the owl's ability to detect a change in source location.     

Activation of NMDA receptors blocks GABAergic inhibition in an in vitro model of epilepsy

The application of tetanic electrical stimuli to the stratum radiatum fibre pathway in the hippocampus in vitro produces an NMDA (N-methyl-D-aspartate) receptor-dependent enhancement of synaptic efficacy. Repeated application of such stimuli produces a progressive enhancement of synaptic efficacy leading to the genesis of spontaneous and stimulation-evoked epileptiform discharges. We have used this in vitro approach to explore the cellular mechanisms which underlie the kindling model of epilepsy. Kindling of the stratum radiatum fibre pathway in vitro induced a progressive, long-lasting reduction of both spontaneous and stimulation-evoked GABAergic (gamma-aminobutyric acid-mediated) inhibitory postsynaptic potentials (i.p.s.ps). The reduction of i.p.s.ps by kindling was associated with a profound decrease in the sensitivity of CA1 pyramidal neurons to ionophoretically applied GABA and an increase in sensitivity to NMDA. The reduction of i.p.s.ps and GABA sensitivity was prevented by kindling in the presence of the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (D-APV). These results demonstrate that kindling-like stimulus patterns produce a reduction of GABAergic inhibition in the hippocampus resulting from a stimulus-induced postsynaptic activation of NMDA receptors. The modulation of GABAergic inhibition by NMDA receptors may cause the synaptic plasticity which underlies the kindling model of epilepsy.