Gabaergic control of rat substantia nigra dopaminergic neurons: Role of globus pallidus and substantia nigra pars reticulata
Gabaergic control of rat substantia nigra dopaminergic neurons: Role of globus pallidus and substantia nigra pars reticulata
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DOI：
10.1016/s0306-4522(98)00356-x
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发表时间：
1999-03-01
期刊：
影响因子：
3.3
通讯作者：
Tepper, JM
中科院分区：
文献类型：
--
作者：
Celada, P;Paladini, CA;Tepper, JM
体内的多巴胺能神经元以三种不同的模式或方式自发放电。先前已表明，黑质多巴胺能神经元的放电模式可通过局部应用GABA(A)和GABA(B)受体拮抗剂进行差异性调节。GABA(A)拮抗剂，如荷包牡丹碱或印防己毒素，可极大地增加多巴胺能神经元的爆发式放电，而GABA(B)拮抗剂则导致从爆发式放电向类似起搏器式放电的适度转变。黑质多巴胺能神经元的三个主要GABA能输入来自纹状体、苍白球以及黑质网状部投射神经元的轴突侧支，它们在体内似乎主要作用于GABA(A)受体（见前文）。在本研究中，我们试图确定GABA(A)拮抗剂作用于哪些传入通路以引起爆发式放电。在氨基甲酸乙酯麻醉的大鼠中，通过单单位细胞外记录研究黑质多巴胺能神经元，同时对苍白球进行药理学诱导的抑制和兴奋。蝇蕈醇诱导的苍白球神经元抑制使黑质多巴胺能神经元放电的规律性增加，同时放电频率略有降低。荷包牡丹碱诱导的苍白球神经元兴奋使爆发式放电显著增加，同时放电频率适度增加。这些放电频率的变化与单突触GABA能苍白球 - 黑质输入所预期的方向相反。对网状部GABA能神经元在苍白球类似操作下的反应进行检查发现，这些神经元的放电频率对苍白球神经元放电频率的变化比多巴胺能神经元敏感得多，且反应方向相反。苍白球抑制使网状部GABA能神经元的放电频率大幅增加，而苍白球兴奋则抑制网状部GABA能神经元的自发活动。这些数据表明，苍白球通过一个涉及黑质网状部GABA能神经元的双突触通路，对黑质多巴胺能神经元的放电频率和模式进行显著控制，并且局部应用荷包牡丹碱诱导多巴胺能神经元爆发式放电的至少一种重要方式是通过解除这种持续性抑制输入的抑制作用。(C) 1999国际脑研究组织。由爱思唯尔科学有限公司出版。
Dopaminergic neurons in vivo fire spontaneously in three distinct patterns or modes. It has previously been shown that the firing pattern of substantia nigra dopaminergic neurons can be differentially modulated by local application of GABA(A) and GABA(B) receptor antagonists. The GABA(A) antagonists, bicuculline or picrotoxin, greatly increase burst firing in dopaminergic neurons whereas GABA(B) antagonists cause a modest shift away from burst firing towards pacemaker-like firing. The three principal GABAergic inputs to nigral dopaminergic neurons arise from striatum, globus pallidus and from the axon collaterals of nigral pars reticulata projection neurons, each of which appear to act in vivo primarily on GABA(A) receptors (see preceding paper). In this study we attempted to determine on which afferent pathway(s) GABA(A) antagonists were acting to cause burst firing. Substantia nigra dopaminergic neurons were studied by single unit extracellular recordings in urethane anesthetized rats during pharmacologically induced inhibition and excitation of globus pallidus. Muscimol-induced inhibition of pallidal neurons produced an increase in the regularity of firing of nigral dopaminergic neurons together with a slight decrease in firing rate. Bicuculline-induced excitation of globus pallidus neurons produced a marked increase in burst firing together with a modest increase in firing rate. These changes in firing rate were in the opposite direction to what would be expected for a monosynaptic GABAergic pallidonigral input. Examination of the response of pars reticulata GABAergic neurons to similar manipulations of globus pallidus revealed that the firing rates of these neurons were much more sensitive to changes in globus pallidus neuron firing rate than dopaminergic neurons and that they responded in the opposite direction. Pallidal inhibition produced a dramatic increase in the firing rate of pars reticulata GABAergic neurons while pallidal excitation suppressed the spontaneous activity of pars reticulata GABAergic neurons.These data suggest that globus pallidus exerts significant control over the firing rate and pattern of substantia nigra dopaminergic neurons through a disynaptic pathway involving nigral pars reticulata GABAergic neurons and that at least one important way in which local application of bicuculline induces burst firing of dopaminergic neurons is by disinhibition of this tonic inhibitory input. (C) 1999 IBRO. Published by Elsevier Science Ltd.