GABAergic modulation of the activity of globus pallidus neurons in primates: In vivo analysis of the functions of GABA receptors and GABA transporters
GABAergic modulation of the activity of globus pallidus neurons in primates: In vivo analysis of the functions of GABA receptors and GABA transporters
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DOI：
10.1152/jn.00068.2005
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发表时间：
2005-08-01
影响因子：
2.5
通讯作者：
Wichmann, T
中科院分区：
文献类型：
--
作者：
Galvan, A;Villalba, RM;Wichmann, T
苍白球外段和内段的神经元（分别为GPe和GPi）从纹状体和邻近苍白球神经元的轴突侧枝接收大量gaba能输入。GABA对苍白质活动的影响取决于GABA受体的突触定位和GABA转运体（GATs）的分布和活性。为了探讨GABA受体和转运体对苍白质功能的贡献，我们在清醒的恒河猴局部显微注射GABA能化合物之前、期间和之后，记录了GPe或GPi单个神经元的活性。分别用muscimol或baclofen激活GABA(A)或GABA(B)受体可抑制苍白球活性。通过同时输注GABA受体拮抗剂gabazine和CGP- 55845，这些作用被逆转。单独给药，拮抗剂没有一致的效果。选择性GAT- 1抑制剂SKF- 89976A和半选择性GAT- 3阻滞剂SNAP-5114的应用降低了苍白球活性。通过微透析测量，两种GAT抑制剂都增加了苍白球中GABA的水平。电镜观察显示，这些转运蛋白位于胶质突和无髓鞘轴突段，但很少位于末梢。我们的研究结果表明，GABA(A)和GABA(B)受体的激活抑制了苍白球两个部分的神经元活动。GAT- 1和GAT- 3参与内源性GABA水平的调节，并可能在调节突触外GABA水平方面发挥重要作用。加上先前的证据表明相当大比例的白质GABA受体位于突触间隙外，我们的实验有力地支持了灵长类苍白质突触外GABA能传递的重要性。
Neurons in the external and internal segment of the globus pallidus ( GPe and GPi, respectively) receive substantial GABAergic inputs from the striatum and through axon collaterals of neighboring pallidal neurons. The effects of GABA on pallidal activity depend on the synaptic localization of GABA receptors and the distribution and activity of GABA transporters ( GATs). To explore the contribution of GABA receptors and transporters to pallidal function, we recorded the activity of single neurons in GPe or GPi before, during, and after local microinjections of GABAergic compounds in awake rhesus monkeys. Activation of GABA(A) or GABA(B) receptors with muscimol or baclofen, respectively, inhibited pallidal activity. These effects were reversed by concomitant infusion of the respective GABA receptor antagonists, gabazine and CGP- 55845. Given alone, the antagonists were without consistent effect. Application of the selective GAT- 1 inhibitor, SKF- 89976A, and the semiselective GAT- 3 blocker, SNAP-5114, decreased pallidal activity. Both GAT inhibitors increased GABA levels in the pallidum, as measured by microdialysis. Electron microscopic observations revealed that these transporters are located on glial processes and unmyelinated axonal segments, but rarely on terminals. Our results indicate that activation of GABA(A) and GABA(B) receptors inhibits neuronal activity in both segments of the pallidum. GAT- 1 and GAT- 3 are involved in the modulation of endogenous GABA levels and may be important in regulating the extrasynaptic levels of GABA. Together with previous evidence that a considerable proportion of pallidal GABA receptors are located outside the synaptic cleft, our experiments strongly support the importance of extrasynaptic GABAergic transmission in the primate pallidum.