Neuronal coupling via connexin36 contributes to spontaneous synaptic currents of striatal medium-sized spiny neurons

Neuronal coupling via connexin36 contributes to spontaneous synaptic currents of striatal medium-sized spiny neurons
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DOI:
10.1002/jnr.21674
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发表时间:
2008-08-01
影响因子:
4.2
通讯作者:
Levine, Michael S.
Levine, Michael S.
中科院分区:
医学3区
文献类型:
--
作者:
Cummings, Damian M.;Yamazaki, Irene;Levine, Michael S.

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间隙连接为神经元之间的电张力耦合提供了一种手段,允许同步活动的产生,这是学习和记忆的重要因素。Connexin36 (Cx36)在很大程度上是神经元特异性的,并为基因操作提供了一个目标,以确定神经元偶联的生理相关性。在纹状体中,Cx36更具体地定位于神经元间群,这为主要投射的中等棘神经元提供了主要的抑制输入。在本研究中,我们研究了基因消融Cx36对纹状体自发突触活动的影响。膜片钳记录了中型棘神经元,中间神经元的主要目标。在Cx36基因敲除小鼠中,兴奋性和抑制性自发突触后电流的频率都降低了。我们还发现,与野生型小鼠相比,在Cx36基因敲除小鼠中,多巴胺受体的激活对gaba能电流的频率有不同的调节,这表明多巴胺在改变中间神经元的偶联中起作用。综上所述,目前的研究结果表明,神经元群体的电耦合对于维持纹状体内正常的化学突触相互作用是重要的。(c) 2008 Wiley-Liss, Inc。
Gap junctions provide a means for electrotonic coupling between neurons, allowing for the generation of synchronous activity, an important contributor to learning and memory. Connexin36 (Cx36) is largely neuron specific and provides a target for genetic manipulation to determine the physiological relevance of neuronal coupling. Within the striatum, Cx36 is more specifically localized to the interneuronal population, which provides the main inhibitory input to the principal projection medium-sized spiny neurons. In the present study, we examined the impact of genetic ablation of Cx36 on striatal spontaneous synaptic activity. Patch-clamp recordings were performed from medium-sized spiny neurons, the primary target of interneurons. In Cx36 knockout mice, the frequencies of both excitatory and inhibitory spontaneous postsynaptic currents were reduced. We also showed that activation of dopamine receptors differentially modulated the frequency of GABAergic currents in Cx36 knockout mice compared with their wild-type littermates, suggesting that dopamine plays a role in altering the coupling of interneurons. Taken together, the present findings demonstrate that electrical coupling of neuronal populations is important for the maintenance of normal chemical synaptic interactions within the striatum. (c) 2008 Wiley-Liss, Inc.