Ionic mechanisms underlying autonomous action potential generation in the somata and dendrites of GABAergic substantia nigra pars reticulata neurons in vitro
Ionic mechanisms underlying autonomous action potential generation in the somata and dendrites of GABAergic substantia nigra pars reticulata neurons in vitro
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DOI：
10.1523/jneurosci.1475-05.2005
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发表时间：
2005-09-07
影响因子：
5.3
通讯作者：
Bevan, MD
中科院分区：
文献类型：
--
作者：
Atherton, JF;Bevan, MD
通过其重复放电，黑质网状部（SNr）的GABA能神经元紧张性地抑制基底神经节的靶核和中脑的多巴胺神经元。由于SNr神经元的重复放电在体外持续存在，因此从大鼠脑切片进行穿孔、全细胞和细胞贴附膜片钳记录，以确定这种活动的机制。SNr神经元的自发活动不受快速突触传递阻断的干扰，表明它在本质上是自主的。一个阈下的，缓慢失活的，电压依赖性的，河豚毒素（TTX）敏感的Na+电流和TTX不敏感的内向电流，部分由Na+介导的负责去极化动作电位（AP）阈值。由小电导Ca 2+依赖性K+（SK）通道介导的apamin敏感性尖峰后超极化对自主活动的精确性至关重要。SK通道被激活，部分，通过Ca 2+流经ω-芋螺毒素GVIA敏感，类2.2电压依赖性Ca 2+通道。虽然Cs+/ZD 7288（4-乙基苯氨基-1，2-二甲基-6-甲基氨基嘧啶氯化物）敏感的超极化激活电流也观察到SNr神经元，他们被激活的电压，一般比自主活动相关的超极化。同时体细胞和树突记录显示，自主产生的AP观察到第一个在索马，然后传播到树突高达120 μ m的体细胞记录网站。自主生成的AP的反向传播是可靠的，没有明显的故障发生率。总之，这些数据表明，基底神经节的静息抑制输出在很大程度上依赖于传递该信号的神经元的固有放电特性。
Through their repetitive discharge, GABAergic neurons of the substantia nigra pars reticulata (SNr) tonically inhibit the target nuclei of the basal ganglia and the dopamine neurons of the midbrain. As the repetitive firing of SNr neurons persists in vitro, perforated, whole-cell and cell-attached patch-clamp recordings were made from rat brain slices to determine the mechanisms underlying this activity. The spontaneous activity of SNr neurons was not perturbed by the blockade of fast synaptic transmission, demonstrating that it was autonomous in nature. A subthreshold, slowly inactivating, voltage-dependent, tetrodotoxin (TTX)-sensitive Na+ current and a TTX-insensitive inward current that was mediated in part by Na+ were responsible for depolarization to action potential (AP) threshold. An apamin-sensitive spike afterhyperpolarization mediated by small-conductance Ca2+-dependent K+ (SK) channels was critical for the precision of autonomous activity. SK channels were activated, in part, by Ca2+ flowing through omega-conotoxin GVIA-sensitive, class 2.2 voltage-dependent Ca2+ channels. Although Cs+/ZD7288 (4-ethylphenylamino-1,2-dimethyl-6-methylaminopyrimidinium chloride)sensitive hyperpolarization-activated currents were also observed in SNr neurons, they were activated at voltages that were in general more hyperpolarized than those associated with autonomous activity. Simultaneous somatic and dendritic recordings revealed that autonomously generated APs were observed first at the soma before propagating into dendrites up to 120 mu m from the somatic recording site. Backpropagation of autonomously generated APs was reliable with no observable incidence of failure. Together, these data suggest that the resting inhibitory output of the basal ganglia relies, in large part, on the intrinsic firing properties of the neurons that convey this signal.