Dutar P, Petrozzino J J, Vu H M, Schmidt M F, Perkel D J
Department of Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6074, USA.
J Neurophysiol. 2000 Nov;84(5):2284-90. doi: 10.1152/jn.2000.84.5.2284.
Glutamate is the predominant excitatory neurotransmitter in the vertebrate CNS. Ionotropic glutamate receptors mediate fast excitatory actions whereas metabotropic glutamate receptors (mGluRs) mediate a variety of slower effects. For example, mGluRs can mediate presynaptic inhibition, postsynaptic excitation, or, more rarely, postsynaptic inhibition. We previously described an unusually slow form of postsynaptic inhibition in one class of projection neuron in the song-control nucleus HVc of the songbird forebrain. These neurons, which participate in a circuit that is essential for vocal learning, exhibit an inhibitory postsynaptic potential (IPSP) that lasts several seconds. Only a portion of this slow IPSP is mediated by GABA(B) receptors. Since these cells are strongly hyperpolarized by agonists of mGluRs, we used intracellular recording from brain slices to investigate the mechanism of this hyperpolarization and to determine whether mGluRs contribute to the slow synaptic inhibition. We report that mGluRs hyperpolarize these HVc neurons by activating G protein-coupled, inwardly-rectifying potassium (GIRK) channels. MGluR antagonists blocked this response and the slow synaptic inhibition. Thus, glutamate can combine with GABA to mediate slow synaptic inhibition by activating GIRK channels in the CNS.
谷氨酸是脊椎动物中枢神经系统中主要的兴奋性神经递质。离子型谷氨酸受体介导快速的兴奋作用，而代谢型谷氨酸受体（mGluRs）介导多种较慢的效应。例如，mGluRs可介导突触前抑制、突触后兴奋，或更罕见的突触后抑制。我们之前描述了鸣禽前脑鸣唱控制核HVC中一类投射神经元中一种异常缓慢的突触后抑制形式。这些神经元参与对发声学习至关重要的神经回路，表现出持续数秒的抑制性突触后电位（IPSP）。这种缓慢的IPSP只有一部分由GABA(B)受体介导。由于这些细胞被mGluRs激动剂强烈超极化，我们利用脑片的细胞内记录来研究这种超极化的机制，并确定mGluRs是否参与缓慢的突触抑制。我们报告称，mGluRs通过激活G蛋白偶联内向整流钾（GIRK）通道使这些HVC神经元超极化。mGluR拮抗剂阻断了这种反应以及缓慢的突触抑制。因此，谷氨酸可与GABA结合，通过激活中枢神经系统中的GIRK通道介导缓慢的突触抑制。
