Ethanol-Sensitive Pacemaker Neurons in the Mouse External Globus Pallidus.
Ethanol-Sensitive Pacemaker Neurons in the Mouse External Globus Pallidus.
复制标题
小鼠外部苍白球中的乙醇敏感起搏器神经元。
DOI：
10.1038/npp.2016.251
复制
发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Lovinger DM
中科院分区：
文献类型：
--
作者：
Abrahao KP;Chancey JH;Chan CS;Lovinger DM
虽然乙醇是最广泛使用的药物之一，但我们仍然缺乏对哪些神经元亚型受到这种药物的影响的充分了解。起搏器神经元对脑回路功能具有强大的控制作用，但乙醇对这些类型的神经元的影响知之甚少。外苍白球（GPe）中的神经元产生起搏器活动，控制基底神经节，与习惯性和强迫性药物使用相关的电路。我们对GPe神经元进行膜片钳记录，发现乙醇溶液剂量依赖性地降低了低频GPe神经元的放电速率，但没有改变高频GPe神经元的放电速率。GABA或谷氨酸受体拮抗剂不能阻断乙醇的作用。GPe由异质的神经元群组成。我们使用Lhx6-EGFP和Npas1-tdTm小鼠菌株鉴定低频神经元。Lhx6和Npas1神经元在乙醇作用下放电减少，但只有Npas1神经元对10 mM乙醇敏感。大电导电压和Ca2+激活的K+ (BK)通道在乙醇对GPe神经元的作用中起关键作用，因为BK通道抑制剂的应用阻断了乙醇诱导的放电减少。在Npas1-tdTm神经元的单通道记录中，乙醇也增加了BK通道打开的概率。此外，GPe的体内电生理记录显示，乙醇减少了大量低频神经元的放电。这些发现表明了乙醇对起搏器神经元的选择性作用是如何发生的，并增强了我们对急性乙醇对基底神经节影响的机制的理解。
Although ethanol is one of the most widely used drugs, we still lack a full understanding of which neuronal subtypes are affected by this drug. Pacemaker neurons exert powerful control over brain circuit function, but little is known about ethanol effects on these types of neurons. Neurons in the external globus pallidus (GPe) generate pacemaker activity that controls basal ganglia, circuitry associated with habitual and compulsive drug use. We performed patch-clamp recordings from GPe neurons and found that bath application of ethanol dose-dependently decreased the firing rate of low-frequency GPe neurons, but did not alter the firing of high-frequency neurons. GABA or glutamate receptor antagonists did not block the ethanol effect. The GPe is comprised of a heterogeneous population of neurons. We used Lhx6-EGFP and Npas1-tdTm mice strains to identify low-frequency neurons. Lhx6 and Npas1 neurons exhibited decreased firing with ethanol, but only Npas1 neurons were sensitive to 10 mM ethanol. Large-conductance voltage and Ca2+-activated K+ (BK) channel have a key role in the ethanol effect on GPe neurons, as the application of BK channel inhibitors blocked the ethanol-induced firing decrease. Ethanol also increased BK channel open probability measured in single-channel recordings from Npas1-tdTm neurons. In addition, in vivo electrophysiological recordings from GPe showed that ethanol decreased the firing of a large subset of low-frequency neurons. These findings indicate how selectivity of ethanol effects on pacemaker neurons can occur, and enhance our understanding of the mechanisms contributing to acute ethanol effects on the basal ganglia.
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影响因子：
4.4
作者：
Jamal, Mostofa;Ameno, Kiyoshi;Kinoshita, Hiroshi
通讯作者：
Kinoshita, Hiroshi
DOI：
10.1073/pnas.1317363111
发表时间：
2014-06-24
影响因子：
11.1
作者：
Bukiya, Anna N.;Kuntamallappanavar, Guruprasad;Dopico, Alex M.
通讯作者：
Dopico, Alex M.
影响因子：
2.5
作者：
Gdowski, MJ;Miller, LE;Houk, JC
通讯作者：
Houk, JC
DOI：
10.1097/01.alc.0000187592.57853.12
发表时间：
2005-11-01
影响因子：
3.2
作者：
Kozell, LB;Hitzemann, R;Buck, KJ
通讯作者：
Buck, KJ
影响因子：
4
作者：
Dopico AM;Bukiya AN;Martin GE
通讯作者：
Martin GE