Acute ethanol modulation of neurocircuit function in the nucleus of the tractus solitarius.
Acute ethanol modulation of neurocircuit function in the nucleus of the tractus solitarius.
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DOI：
10.1016/j.brainresbull.2017.07.019
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发表时间：
2018-04
影响因子：
3.8
通讯作者：
Silberman Y
中科院分区：
文献类型：
--
作者：
Aimino MA;Coker CR;Silberman Y
孤束核(NTS)是一个对许多生理过程至关重要的脑干区域，与包括酒精在内的多种滥用药物的成瘾有关。尽管如此，乙醇调节NTS神经回路活动的机制还没有得到很好的表征，还没有在酒精使用障碍的小鼠模型中利用电生理学方法进行检验。为了开始解决这一知识差距，我们试图使用全细胞和细胞附着记录来确定急性乙醇对GABA能和谷氨酸能神经传递的作用机制，以及对成年雄性乙醇幼稚小鼠NTS动作电位放电的作用机制。50 mM乙醇浴可显著增加半数受试神经元自发抑制性突触后电流事件的频率，同时增加这些事件的幅度。这一发现表明，在NTS中，乙醇对GABA能传递的作用可能是突触前机制，在NTS神经元亚群中可能是突触后机制。在测试的大多数但不是所有NTS神经元中，施加乙醇进一步与动作电位放电显著减少有关。乙醇可引起自发性兴奋性突触后电流频率显著降低，提示乙醇对NTS谷氨酸能信号也有一定程度的抑制作用。有趣的是，体内乙醇暴露(4g/kg ip)通过免疫组织化学方法增强了c-fos与酪氨酸羟化酶的共存，表明急性乙醇暴露可能激活了NTS去甲肾上腺素神经元。尽管还需要进一步的工作，但目前的数据表明，急性乙醇可能会增强局部NTS回路中的GABA能信号，从而解除对NTS去甲肾上腺素神经元的抑制。这一发现对于理解NTS在酒精中毒发生发展中的作用具有重要意义。
The nucleus of the tractus solitarius (NTS) is a brain stem region critical to many physiologic processes and has been implicated in addiction to multiple classes of abused drugs, including alcohol (EtOH). That said, the mechanism by which EtOH modulates NTS neurocircuit activity is not well characterized and has yet to be examined utilizing electrophysiologic methods in mouse models of alcohol use disorders. To begin to address this gap in knowledge, we sought to use whole-cell and cell-attached recordings to determine the mechanism of acute EtOH action on GABAergic and glutamatergic neurotransmission, as well as on action potential firing in the NTS of adult male, EtOH naive mice. Bath application of EtOH (50 mM) significantly enhanced the frequency of spontaneous inhibitory postsynaptic current events, while increasing the amplitude of these events in half of the neurons tested. This finding suggests a presynaptic mechanism of EtOH action on GABAergic transmission in the NTS as well as a postsynaptic mechanism in subsets of NTS neurons. EtOH application was further associated with a significant decrease in action potential firing in most, but not all, NTS neurons tested. EtOH induced a small but significant decrease in spontaneous excitatory postsynaptic current frequency, indicating that EtOH may also inhibit NTS glutamatergic signaling to some degree. Intriguingly, in vivo EtOH exposure (4 g/kg IP) enhanced c-FOS colocalization with tyrosine hydroxylase via immunohistochemical methods, indicating that NTS norepinephrine neurons may be activated by acute EtOH exposure. Although future work is needed, the current data indicate that acute EtOH may enhance GABAergic signaling in local NTS circuits resulting in disinhibition of NTS norepinephrine neurons. Such a finding has important implications in understanding the role of the NTS in the development of alcoholism.
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影响因子：
56.9
作者：
Olson, VG;Heusner, CL;Palmiter, RD
通讯作者：
Palmiter, RD
扩展杏仁核中的去肾上腺素能传播：在持久的药物戒酒期间，在毒品寻求和复发中的作用。
影响因子：
3.1
作者：
Smith, Rachel J.;Aston-Jones, Gary
通讯作者：
Aston-Jones, Gary
影响因子：
7.6
作者：
Lowery-Gionta, Emily G.;Marcinkiewcz, Catherine A.;Kash, Thomas L.
通讯作者：
Kash, Thomas L.
DOI：
10.1097/00000374-200006000-00009
发表时间：
2000-06-01
影响因子：
3.2
作者：
Thiele, TE;Cubero, I;Bernstein, IL
通讯作者：
Bernstein, IL
影响因子：
3.3
作者：
Xiao, C.;Ye, J. -H.
通讯作者：
Ye, J. -H.