Subthalamic stimulation-induced synaptic responses in substantia nigra pars compacta dopaminergic neurons in vitro
Subthalamic stimulation-induced synaptic responses in substantia nigra pars compacta dopaminergic neurons in vitro
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DOI：
10.1152/jn.1999.82.2.925
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发表时间：
1999-08-01
影响因子：
2.5
通讯作者：
Tepper, JM
中科院分区：
文献类型：
--
作者：
Iribe, Y;Moore, K;Tepper, JM
丘脑底核(STN)是黑质多巴胺能神经元兴奋性谷氨酸能输入的主要来源之一，但刺激STN对细胞外记录的黑质多巴胺能神经元既有兴奋作用，又有抑制作用。本实验旨在确定兴奋性和抑制性效应的来源。刺激STN后，在矢状面附近脑片的黑质致密区多巴胺能神经元细胞内记录到突触电位。在存在和不存在GABA和谷氨酸受体拮抗剂的情况下，分析突触电位的起始潜伏期、幅度、持续时间和翻转电位。在多巴胺能神经元中，STN诱发的去极化突触反应在大约-31 mV时逆转，介于兴奋性和抑制性突触后电位(EPSP和IPSP)之间。用荷包牡丹碱阻断GABA(A)受体可使翻转电位正移至接近0 mV，提示刺激STN可同时诱发EPSP和IPSP。谷氨酸受体拮抗剂6-氰基-7-硝基-2，3-二酮可阻断这两种突触反应。记录前3d单侧切断纹状体和苍白球纤维可消除刺激STN对苍白球和/或纹状体通路抑制纤维的混杂影响。在横断动物脑片中，STN诱发的多巴胺能神经元突触反应的反转电位约为-30 mV。荷包牡丹碱可使IPSP的翻转电位向正常动物的5 mV左右移动，提示IPSP的来源位于黑质。这些结果表明，电刺激STN在黑质多巴胺能神经元中引起EPSP-IPSP混合反应，这是由于STN与致密质多巴胺能神经元之间的兴奋性单突触和抑制性多突触联系共同激活所致。EPSP来源于STN的直接单突触兴奋性谷氨酸能输入。IPSP以多突触的形式出现。这很可能是通过STN诱发的对黑质网状部GABA能神经元的兴奋，从而产生前馈GABA(A)介导的通过抑制黑质内轴突侧支对多巴胺能神经元的抑制。
The subthalamic nucleus (STN) is one of the principal sources of excitatory glutamatergic input to dopaminergic neurons of the substantia nigra, yet stimulation of the STN produces both excitatory and inhibitory effects on nigral dopaminer- gic neurons recorded extracellularly in vivo. The present experiments were designed to determine the sources of the excitatory and inhibitory effects. Synaptic potentials were recorded intracellularly from substantia:nigra pars compacta dopaminergic neurons in parasagittal slices in response to stimulation of the STN. Synaptic potentials were analyzed for onset latency, amplitude, duration, and reversal potential in the presence and absence of GABA and glutamate receptor antagonists. STN-evoked depolarizing synaptic responses in dopaminergic neurons reversed at approximately -31 mV, intermediate between the expected reversal potential for an excitatory and an inhibitory postsynaptic potential (EPSP and IPSP). Blockade of GABA(A) receptors with bicuculline caused a positive shift in the reversal potential to near 0 mV, suggesting that STN stimulation evoked a near simultaneous EPSP and IPSP. Both synaptic responses were blocked by application of the glutamate receptor antagonist, 6-cyano-7-nitroquinoxalene-2,3-dione. The confounding influence of inhibitory fibers of passage from globus pallidus and/or striatum by STN stimulation was eliminated by unilaterally transecting striatonigral and pallidonigral fibers 3 days before recording. The reversal potential of STN-evoked synaptic responses in dopaminergic neurons in slices from transected animals was approximately -30 mV. Bath application of bicuculline shifted the reversal potential to similar to 5 mV as it did in intact animals, suggesting that the source of the IPSP was within substantia nigra. These data indicate that electrical stimulation of the STN elicits a mixed EPSP-IPSP in nigral dopaminergic neurons due to the coactivation of an excitatory monosynaptic and an inhibitory polysynaptic connection between the STN and the dopaminergic neurons of substantia nigra pars compacta. The EPSP arises from a direct monosynaptic excitatory glutamatergic input from the STN. The IPSP arises polysynaptically. most likely through STN-evoked excitation of GABAergic neurons in substantia nigra pars reticulata, which produces feed-forward GABA(A)-mediated inhibition of dopaminergic neurons through inhibitory intranigral axon collaterals.