Presynaptic modulation by metabotropic glutamate receptors of excitatory and inhibitory synaptic inputs to hypothalamic magnocellular neurons.
Presynaptic modulation by metabotropic glutamate receptors of excitatory and inhibitory synaptic inputs to hypothalamic magnocellular neurons.
复制标题
代谢型谷氨酸受体对下丘脑大细胞神经元的兴奋性和抑制性突触输入的突触前调节。
DOI：
10.1152/jn.1997.77.2.527
复制
发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Tasker,JG
中科院分区：
文献类型：
--
作者：
Schrader,LA;Tasker,JG
洛杉矶，施拉德。和J. G. Tasker.下丘脑大细胞神经元兴奋性和抑制性突触输入的代谢型谷氨酸受体的突触前调制.神经生理学杂志77：527-536，1997.在急性下丘脑脑片上，用全细胞膜片钳和微电极记录技术研究了代谢型谷氨酸受体（mGluRs）激活对下丘脑视上核（SON）大细胞神经元突触传入的影响。mGluR激动剂反式-（±）-1-氨基-1，3-环戊烷二羧酸的应用（trans-ACPD，100 μM）在20%的细胞中引起自发兴奋性突触后电位（EPSP）和兴奋性突触后电流（EPSC）频率增加，在正常培养液中，50%的细胞出现自发性抑制性突触后电位（IPSPs）和抑制性突触后电流（IPSC）。自发性EPSP/EPSC和IPSP/IPSC频率的增加被河豚毒素（TTX）阻断，表明mGluRs起兴奋突触前谷氨酸能和GABA能神经元的胞体/树突的作用。选择性I组受体激动剂（RS）-3，5-二羟基苯甘氨酸（50 μM）模拟trans-ACPD的突触前体细胞/树突效应，表明负责增加尖峰依赖性谷氨酸和γ-氨基丁酸（GABA）释放的突触前体细胞/树突受体属于I组mGluRs。在TTX的存在下，trans-ACPD导致16个细胞中的13个中的微型EPSC的频率降低（高达90%），并且在测试的16个细胞中的10个中的微型IPSC的频率降低（高达80%）。在反式ACPD中，微型EPSC和IPSC振幅通常不改变，这表明位于突触前谷氨酸能和GABA能终末的代谢型受体的激活导致SON大细胞神经元上的递质释放减少。（100-250 μM），一种选择性III族受体激动剂，模拟反式-ACPD在突触前末梢的作用，将微型EPSC和IPSC的频率降低高达85%，而不影响其振幅。因此，SON中突触前谷氨酸和GABA末端的代谢型受体属于III组mGluRs。第III组受体拮抗剂（S）-2-氨基-2-甲基-4-膦酰基丁酸可增强电刺激诱发的EPSC，表明突触前代谢型受体被内源性谷氨酸的释放激活。这些数据表明，下丘脑中的mGluRs在突触前胞体/树突和突触前末梢具有相反的作用。I组受体（mGluR 1和/或mGluR 5）突触前体/树突上的激活导致尖峰依赖性递质释放的增加，而III组受体（mGluR 4，7和/或8）突触前末梢上的激活抑制谷氨酸和GABA释放到SON神经元。化学鉴定的SON催产素和加压素神经元之间的mGluR激活效应没有差异。
Schrader, L. A. and J. G. Tasker.Presynaptic modulation by metabotropic glutamate receptors of excitatory and inhibitory synaptic inputs to hypothalamic magnocellular neurons.J. Neurophysiol.77: 527–536, 1997. The effects of activation of metabotropic glutamate receptors (mGluRs) on synaptic inputs to magnocellular neurons of the hypothalamic supraoptic nucleus (SON) were studied with the use of whole cell patch-clamp and microelectrode recordings in acute hypothalamic slices. Application of the mGluR agonisttrans-(±)-1-amino-1,3-cyclopentane dicarboxylic acid (trans-ACPD, 100 μM) elicited an increase in the frequency of spontaneous excitatory postsynaptic potentials (EPSPs) and excitatory postsynaptic currents (EPSCs) in 20% of the cells, and of spontaneous inhibitory postsynaptic potentials (IPSPs) and inhibitory postsynaptic currents (IPSCs) in 50% of the cells tested in normal medium. The increased frequency of spontaneous EPSPs/EPSCs and IPSPs/IPSCs was blocked by tetrodotoxin (TTX), indicating that mGluRs act to excite the somata/dendrites of presynaptic glutamatergic and GABAergic neurons. (RS)-3,5-dihydroxyphenylglycine (50 μM), a selective group I receptor agonist, mimicked the presynaptic somatic/dendritic effects oftrans-ACPD, suggesting that the presynaptic somatic/dendritic receptors responsible for increased spike-dependent glutamate and γ-aminobutyric acid (GABA) release belong to the group I mGluRs. In the presence of TTX,trans-ACPD caused a decrease in the frequency of miniature EPSCs (up to 90%) in 13 of 16 cells, and a decrease in the frequency of miniature IPSCs (up to 80%) in 10 of 16 cells tested. Miniature EPSC and IPSC amplitudes usually did not change intrans-ACPD, suggesting that activation of metabotropic receptors located at presynaptic glutamatergic and GABAergic terminals led to a reduction in transmitter release onto SON magnocellular neurons.l(+)-2-amino-4-phosphonobutyric acid (100–250 μM), a selective group III receptor agonist, mimicked the effects oftrans-ACPD at presynaptic terminals, decreasing the frequency of miniature EPSCs and IPSCs by up to 85% without affecting their amplitude. Thus the metabotropic receptors at presynaptic glutamate and GABA terminals in the SON belong to group III mGluRs. EPSCs evoked by electrical stimulation were enhanced by the group III receptor antagonist (S)-2-amino-2-methyl-4-phosphonobutanoic acid, suggesting that presynaptic metabotropic receptors are activated by the release of endogenous glutamate. These data indicate that mGluRs in the hypothalamus have opposing actions at presynaptic somata/dendrites and at presynaptic terminals. Activation of group I receptors (mGluR1 and/or mGluR5) on presynaptic somata/dendrites led to an increase in spike-dependent transmitter release, whereas activation of the group III receptors (mGluR4, 7, and/or 8) on presynaptic terminals suppressed glutamate and GABA release onto SON neurons. No diffferences were seen in the effects of mGluR activation between immunohistochemically identified oxytocin and vasopressin neurons of the SON.