Dopamine Receptors Differentially Control Binge Alcohol Drinking-Mediated Synaptic Plasticity of the Core Nucleus Accumbens Direct and Indirect Pathways
Dopamine Receptors Differentially Control Binge Alcohol Drinking-Mediated Synaptic Plasticity of the Core Nucleus Accumbens Direct and Indirect Pathways
复制标题
DOI：
10.1523/jneurosci.3845-16.2017
复制
发表时间：
2017-05-31
影响因子：
5.3
通讯作者：
Martin, Gilles E.
中科院分区：
文献类型：
--
作者：
Ji, Xincai;Saha, Sucharita;Martin, Gilles E.
暴饮暴食是一种以快速重复饮酒为特征的行为，在年轻人中最为普遍，是过量饮酒和酒精依赖的危险因素。尽管突触可塑性的改变被认为有助于这种行为，但目前几乎没有证据表明情况确实如此。我们使用黑暗饮酒（DID）作为酗酒模型，通过将膜片钳记录与钙成像和光遗传学相结合，评估其对伏隔核（NAc）中型多棘神经元（MSN）的尖峰时间依赖性可塑性（STDP）的影响。每天酗酒两周后，突触可塑性发生了深刻的改变。表达多巴胺 D1 受体的 MSN 中的 STDP 从尖峰时间依赖性长期抑制 (tLTD)（幼稚雄性小鼠可塑性的主要形式）转变为 DID 小鼠中的尖峰时间依赖性长期增强 (tLTP)，这种效应在 4 μM SCH23390（一种多巴胺 D1 受体拮抗剂）存在下完全逆转。在推测表达多巴胺 D2 受体的 MSN 中，tLTP（幼稚小鼠可塑性的主要形式）在 DID 小鼠中受到抑制。有趣的是，1 μM 舒必利（一种 D2 受体拮抗剂）可恢复 tLTP。尽管我们没有观察到 AMPA 和 NMDA 受体特性的改变，但我们发现皮层和杏仁核输入处的 AMPA/NMDA 比率增加，但海马输入处没有增加。此外，DID 对 STDP 的影响还伴随着较低的树突钙瞬变。这些数据表明，无论这些神经元属于直接通路还是间接通路，多巴胺在介导酗酒对 NAc MSN 突触可塑性影响中的作用存在显着差异。
Binge alcohol drinking, a behavior characterized by rapid repeated alcohol intake, is most prevalent in young adults and is a risk factor for excessive alcohol consumption and alcohol dependence. Although the alteration of synaptic plasticity is thought to contribute to this behavior, there is currently little evidence that this is the case. We used drinking in the dark (DID) as a model of binge alcohol drinking to assess its effects on spike timing-dependent plasticity (STDP) in medium spiny neurons (MSNs) of the core nucleus accumbens (NAc) by combining patch-clamp recordings with calcium imaging and optogenetics. After 2 weeks of daily alcohol binges, synaptic plasticity was profoundly altered. STDP in MSNs expressing dopamine D1 receptors shifted from spike-timing-dependent long-term depression (tLTD), the predominant form of plasticity in naive male mice, to spike-timing-dependent long-term potentiation (tLTP) in DID mice, an effect that was totally reversed in the presence of 4 mu M SCH23390, a dopamine D1 receptor antagonist. In MSNs presumably expressing dopamine D2 receptors, tLTP, the main form of plasticity in naive mice, was inhibited in DID mice. Interestingly, 1 mu M sulpiride, a D2 receptor antagonist, restored tLTP. Although we observed no alterations of AMPA and NMDA receptor properties, we found that the AMPA/NMDA ratio increased at cortical and amygdaloid inputs but not at hippocampal inputs. Also, DID effects on STDP were accompanied by lower dendritic calcium transients. These data suggest that the role of dopamine in mediating the effects of binge alcohol drinking on synaptic plasticity of NAc MSNs differs markedly whether these neurons belong to the direct or indirect pathways.