Nigral GABAergic inhibition upon mesencephalic dopaminergic cell groups in rats

Nigral GABAergic inhibition upon mesencephalic dopaminergic cell groups in rats
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DOI:
10.1111/j.0953-816x.2004.03337.x
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发表时间:
2004-05-01
影响因子:
3.4
通讯作者:
Takakusaki, K
Takakusaki, K
中科院分区:
医学3区
文献类型:
--
作者:
Saitoh, K;Isa, T;Takakusaki, K

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在Wistar大鼠中脑切片制备中,研究了γ -氨基丁酸(GABA)介导的黑质网状部(SNr)对中脑多巴胺能神经元的突触抑制作用。采用全细胞膜片钳记录位于脑后野(22)、黑质致密部(47)和腹侧被盖区(24)的多巴胺能神经元(93)的突触电位/电流。在嗜离子性谷氨酸受体拮抗剂存在的情况下,电刺激SNr诱导83个神经元的抑制性突触后电位(IPSPs)和/或电流(IPSCs)。ipsp /IPSCs分为早期和晚期两部分。早期IPSPs/IPSCs是由氯离子电流通过GABA(A)受体介导的。钾电流通过GABA(B)受体介导晚期IPSPs/IPSCs的形成。GABA(A)-和GABA(B)- ipsp均被频率在25 ~ 200 Hz之间的重复刺激放大。该频率范围涵盖了体内信噪比神经元的放电频率。观察到GABA(B)受体拮抗剂的应用增加了GABA(a)- ipsp的振幅。放大之后是反弹去极化,引起多巴胺能神经元的短暂放电。ipsp的这些特性在所有三个多巴胺能核中都是共同的。这些结果表明,突触后GABA(A)-和GABA(B)-抑制分别有助于多巴胺能神经元兴奋性的短暂性和持久性改变。这些突触后机制可能反过来受到突触前GABA(B)抑制的调节。神经gaba能输入可能对中脑多巴胺能系统的背景兴奋性提供时空调节。
Synaptic inhibition from the substantia nigra pars reticulata (SNr) to the mesencephalic dopaminergic neurons, which was mediated by gamma (gamma)-amino-butyric acid (GABA), was investigated in a midbrain slice preparation of Wistar rats. Whole-cell patch-clamp recordings were used to record synaptic potentials/currents from the dopaminergic neurons (n = 93) located in the retrorubral field (n = 22), the substantia nigra pars compacta (n = 47) and the ventral tegmental area (n = 24). In the presence of ionotropic glutamate receptor antagonists electrical stimulation of the SNr induced inhibitory postsynaptic potentials (IPSPs) and/or currents (IPSCs) in 83 neurons. The IPSPs/IPSCs were comprised early and late components. The early IPSPs/IPSCs were mediated by chloride currents through GABA(A) receptors. The late IPSPs/IPSCs were mediated by potassium currents through GABA(B) receptors. Both GABA(A)- and GABA(B)-IPSPs were amplified by repetitive stimuli with frequencies between 25 and 200 Hz. This frequency range covers the firing frequencies of SNr neurons in vivo. It was observed that an application of a GABA(B) receptor antagonist increased the amplitude of the GABA(A)-IPSPs. The amplification was followed by a rebound depolarization that induced transient firing of dopaminergic neurons. These properties of the IPSPs were common in all of the three dopaminergic nuclei. These results suggest that postsynaptic GABA(A)- and GABA(B)-inhibition contribute to transient and persistent alternations of the excitability of dopaminergic neurons, respectively. These postsynaptic mechanisms may be, in turn, regulated by presynaptic GABA(B)-inhibition. Nigral GABAergic input may provide the temporospatial regulation of the background excitability of mesencephalic dopaminergic systems.