BK channels mediate dopamine inhibition of firing in a subpopulation of core nucleus accumbens medium spiny neurons.
BK channels mediate dopamine inhibition of firing in a subpopulation of core nucleus accumbens medium spiny neurons.
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DOI：
10.1016/j.brainres.2014.09.015
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发表时间：
2014-11-07
期刊：
影响因子：
2.9
通讯作者：
Martin, Gilles E.
中科院分区：
文献类型：
--
作者：
Ji, Xincai;Martin, Gilles E.
多巴胺是介导药物滥用的奖赏特性的关键神经递质，被广泛认为通过调节丘脑核（NAcc）中棘神经元（MSNs）的神经元活动来发挥其某些作用。虽然它对突触传递的影响已经有了很好的记录，但它对内在神经元兴奋性的调节却知之甚少。在这项研究中，我们研究了急性多巴胺对核心神经元MSNs诱发放电的细胞机制。我们发现，0.5 μM A-77636和10 μM喹吡罗，多巴胺D1（DR 1 s）和D2受体（D2 Rs）激动剂，分别显着抑制MSN诱发的动作电位。仅在约25%的所有神经元中观察到这种效应，与尖峰时间依赖性（STDP）长时程增强（tLTP）有关，但与长时程抑制（tLTD）无关。多巴胺通过损害阈下去极化抑制诱发放电，而不是通过改变动作电位本身。电压钳模式记录显示，所有MSN表达快速（IA），缓慢失活延迟整流（Idr），大电导电压和钙激活钾（BK）通道。虽然A-77636和喹吡罗增强IA，但0.5 μM phrixotoxin-1选择性阻断其对诱发放电无影响。相反，将组织暴露于低浓度TEA和10 μM paxilline（一种选择性BK通道阻断剂），可阻止D1 R激动剂抑制MSN放电。这一结果表明，多巴胺抑制MSN射击通过BK通道在一个亚群的核心神经元MSN专门与尖峰定时依赖性长时程增强。
Dopamine, a key neurotransmitter mediating the rewarding properties of drugs of abuse, is widely believed to exert some of its effects by modulating neuronal activity of nucleus accumbens (NAcc) medium spiny neurons (MSNs). Although its effects on synaptic transmission have been well documented, its regulation of intrinsic neuronal excitability is less understood. In this study, we examined the cellular mechanisms of acute dopamine effects on core accumbens MSNs evoked firing. We found that 0.5 μM A-77636 and 10 μM quinpirole, dopamine D1 (DR1s) and D2 receptor (D2Rs) agonists, respectively, markedly inhibited MSN evoked action potentials. This effect, observed only in about 25% of all neurons, was associated with spike-timing-dependent (STDP) long-term potentiation (tLTP), but not long-term depression (tLTD). Dopamine inhibited evoked firing by compromising subthreshold depolarization, not by altering action potentials themselves. Recordings in voltage-clamp mode revealed that all MSNs expressed fast (IA), slowly inactivating delayed rectifier (Idr), and large conductance voltage- and calcium-activated potassium (BKs) channels . Although A-77636 and quinpirole enhanced IA, its selective blockade by 0.5 μM phrixotoxin-1 had no effect on evoked firing. In contrast, exposing tissue to low TEA concentrations and to 10 μM paxilline, a selective BK channel blocker, prevented D1R agonist from inhibiting MSN firing. This result indicates that dopamine inhibits MSN firing through BK channels in a subpopulation of core accumbens MSNs exclusively associated with spike-timing-dependent long-term potentiation.
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影响因子：
16.2
作者：
Lüscher C;Malenka RC
通讯作者：
Malenka RC
新规则管理着核心核核核核中棘神经元中的突触可塑性。
DOI：
10.1111/ejn.12002
发表时间：
2012-12
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Ji X;Martin GE
通讯作者：
Martin GE
影响因子：
25
作者：
Aizman, O;Brismar, H;Aperia, A
通讯作者：
Aperia, A
影响因子：
7.3
作者：
Diochot, S;Drici, MD;Lazdunski, M
通讯作者：
Lazdunski, M
影响因子：
5.3
作者：
Martin, G;Puig, S;Treistman, S
通讯作者：
Treistman, S