Electrophysiological and Pharmacological Properties of Locomotor Activity-Related Neurons in cfos-EGFP Mice

Electrophysiological and Pharmacological Properties of Locomotor Activity-Related Neurons in cfos-EGFP Mice
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DOI:
10.1152/jn.00265.2009
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发表时间:
2009-12-01
影响因子:
2.5
通讯作者:
Jordan, Larry M.
Jordan, Larry M.
中科院分区:
医学3区
文献类型:
--
作者:
Dai, Yue;Carlin, Kevin P.;Jordan, Larry M.

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戴 Y、卡林 KP、李 Z、麦克马洪 DG、布朗斯通 RM、乔丹 LM。 cfos-EGFP 小鼠运动活动相关神经元的电生理学和药理学特性。 《神经生理学杂志》102:3365-3383,2009 年。首次发表于 2009 年 9 月 30 日; doi:10.1152/jn.00265.2009.尽管已知运动是由脊髓神经元网络产生的,但对这些神经元特性的了解仍然有限。使用表达由 c-fos 启动子驱动的增强型绿色荧光蛋白 (EGFP) 的新生转基因小鼠,我们在接受运动任务或药物混合物 [N-甲基-D-天冬氨酸、血清素 (5-HT)、多巴胺和乙酰胆碱 (ACh)] 的动物脊髓切片中观察到 EGFP 阳性神经元。通过对神经元进行电刺激,也可以在背根神经节神经元中诱导 EGFP 的活性依赖性表达。游泳 60-90 分钟后,从 T-12 至 L-4 节段切片的 VII、VIII 和 X 层中的 EGFP+ 神经元进行全细胞膜片钳记录。 EGFP+ 神经元 (n = 55) 根据其对去极化阶跃电流的反应可分为三种类型:单尖峰、阶段性放电和强直性放电。在这些神经元中观察到的膜特性包括超极化激活的内向电流 (29/55)、抑制后反弹 (11/55) 和持续内向电流 (31/55)。 10-40μM 5-HT和/或ACh的浴应用增加了神经元的兴奋性或输出,同时电压阈值超极化和膜电位的变化。 5-HT 还增加了输入电阻,降低了后超极化 (AHP),并引起膜振荡,而 ACh 降低了输入电阻并增加了 AHP。在这项研究中,我们展示了一种识别运动活跃神经元的新方法。我们的结果表明 EGFP+ 神经元是中间神经元的异质群体。 5-HT 和 ACh 对这些神经元的作用提供了对这些递质调节的神经元特性的深入了解,以产生运动。
Dai Y, Carlin KP, Li Z, McMahon DG, Brownstone RM, Jordan LM. Electrophysiological and pharmacological properties of locomotor activity-related neurons in cfos-EGFP mice. J Neurophysiol 102: 3365-3383, 2009. First published September 30, 2009; doi:10.1152/jn.00265.2009. Although locomotion is known to be generated by networks of spinal neurons, knowledge of the properties of these neurons is limited. Using neonatal transgenic mice that express enhanced green fluorescent protein (EGFP) driven by the c-fos promoter, we visualized EGFP-positive neurons in spinal cord slices from animals that were subjected to a locomotor task or drug cocktail [N-methyl-D-aspartate, serotonin (5-HT), dopamine, and acetylcholine (ACh)]. The activity-dependent expression of EGFP was also induced in dorsal root ganglion neurons with electrical stimulation of the neurons. Following 60-90 min of swimming, whole cell patch-clamp recordings were made from EGFP+ neurons in laminae VII, VIII, and X from slices of segments T-12 to L-4. The EGFP+ neurons (n = 55) could be classified into three types based on their responses to depolarizing step currents: single spike, phasic firing, and tonic firing. Membrane properties observed in these neurons include hyperpolarization-activated inward currents (29/55), postinhibitory rebound (11/55), and persistent-inward currents (31/55). Bath application of 10-40 mu M 5-HT and/or ACh increased neuronal excitability or output with hyperpolarization of voltage threshold and changes in membrane potential. 5-HT also increased input resistance, reduced the afterhyperpolarization (AHP), and induced membrane oscillations, whereas ACh reduced the input resistance and increased the AHP. In this study, we demonstrate a new way of identifying neurons active in locomotion. Our results suggest that the EGFP+ neurons are a heterogeneous population of interneurons. The actions of 5-HT and ACh on these neurons provide insights into the neuronal properties modulated by these transmitters for generation of locomotion.