GABAergic afferents activate both GABAA and GABAB receptors in mouse substantia nigra dopaminergic neurons in vivo.
GABAergic afferents activate both GABAA and GABAB receptors in mouse substantia nigra dopaminergic neurons in vivo.
复制标题
DOI：
10.1523/jneurosci.2387-08.2008
复制
发表时间：
2008-10-08
期刊：
影响因子：
--
通讯作者：
Tepper JM
中科院分区：
文献类型：
--
作者：
Brazhnik E;Shah F;Tepper JM
大多数黑质体内电生理学研究都采用了大鼠。最近，由于可以利用各种转基因菌株来鉴定各种通道和蛋白质在神经元功能中的作用，因此越来越多地使用小鼠进行体外神经生理学研究，因此获得小鼠体内反应的数据以验证体外结果反映的系统功能与在大鼠中充分研究的系统功能相当至关重要。大鼠黑质多巴胺能神经元通过刺激来自纹状体、苍白球或网状部的传入神经而产生的抑制反应已被证明主要或完全由 GABAA 受体介导。考虑到体外大鼠多巴胺能神经元中 GABAB 受体的大量表达和 GABAB 突触反应的普遍出现，这是令人费解的。在本研究中，我们研究了 C57BL/6J 小鼠黑质多巴胺能神经元的电诱发 GABA 能抑制。三种主要 GABA 能输入的刺激引发了比大鼠更强、更持久的抑制反应。早期抑制是 GABAA 介导的，而后期成分（在大鼠中不存在）是 GABAB 介导的，并通过 GABA 摄取抑制选择性增强。与苍白球或黑质网状部的抑制相比，纹状体诱发的抑制表现出较慢的起效和较弱的初始成分。这些结果的讨论涉及大鼠和小鼠大脑的大小和神经元密度的差异，以及来自三个 GABA 能传入神经的突触接触的不同部位。
Most in vivo electrophysiological studies of substantia nigra have employed rats. With the recent proliferation of the use of mice for in vitro neurophysiological studies due to the availability of various genetically modified strains to identify the roles of various channels and proteins in neuronal function, it is crucial to obtain data on in vivo responses in mice to verify that the in vitro results reflect functioning of systems comparable to those that have been well studied in rat. Inhibitory responses of rat nigral dopaminergic neurons by stimulation of afferents from striatum, globus pallidus or pars reticulata have been shown to be mediated predominantly or exclusively by GABAA receptors. This is puzzling given the substantial expression of GABAB receptors and the ubiquitous appearance of GABAB synaptic responses in rat dopaminergic neurons in vitro. In the present study we studied electrically evoked GABAergic inhibition in nigral dopaminergic neurons in C57BL/6J mice. Stimulation of the three major GABAergic inputs elicited stronger and longer lasting inhibitory responses than those seen in rats. The early inhibition was GABAA mediated, whereas the later component, absent in rats, was GABAB mediated and selectively enhanced by GABA uptake inhibition. Striatal-evoked inhibition exhibited a slower onset and a weaker initial component compared to inhibition from globus pallidus or substantia nigra pars reticulata. These results are discussed with respect to differences in the size and neuronal density of the rat and mouse brain, and the different sites of synaptic contact of the synapses from the three GABAergic afferents.