Synaptic Plasticity and its Modulation by Alcohol.
Synaptic Plasticity and its Modulation by Alcohol.
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DOI：
10.3233/bpl-190089
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发表时间：
2020-12-29
期刊：
影响因子：
--
通讯作者：
Mandyam CD
中科院分区：
文献类型：
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作者：
Avchalumov Y;Mandyam CD
酒精是最古老的药物之一，具有镇静/催眠作用，酒精滥用和酒精使用障碍 (AUD) 仍然是主要的公共卫生问题。 AUD 被强烈表明是一种脑部疾病，而酒精在大脑中产生作用的分子和细胞机制现在才刚刚开始被了解。在大脑中，突触可塑性或突触的增强或减弱可以通过各种刺激范例来增强或减弱。突触可塑性被认为负责学习和记忆细胞机制中的重要过程。长时程增强 (LTP) 是突触可塑性的一种形式，通过 N-甲基-D-天冬氨酸型谷氨酸受体（NMDAR 或 GluN）依赖和独立机制发生。特别是，NMDAR 是酒精的主要目标，并且与不同类型的学习和记忆有关。因此，了解酒精对谷氨酸能信号介导的突触可塑性和传递的影响变得越来越重要，这将有助于我们了解谷氨酸能系统在AUD中的重要贡献。在本综述的第一部分，我们将简要讨论背侧纹状体、新皮质和海马长期突触可塑性的机制。在第二部分中，我们将讨论酒精（乙醇，EtOH）如何调节这三个大脑区域的长期突触可塑性，主要来自神经生理学和电生理学研究。总而言之，了解酒精引起的脑功能变化的机制可能会导致开发出更有效的治疗药物来降低 AUD。
Alcohol is one of the oldest pharmacological agents used for its sedative/hypnotic effects, and alcohol abuse and alcohol use disorder (AUD) continues to be major public health issue. AUD is strongly indicated to be a brain disorder, and the molecular and cellular mechanism/s by which alcohol produces its effects in the brain are only now beginning to be understood. In the brain, synaptic plasticity or strengthening or weakening of synapses, can be enhanced or reduced by a variety of stimulation paradigms. Synaptic plasticity is thought to be responsible for important processes involved in the cellular mechanisms of learning and memory. Long-term potentiation (LTP) is a form of synaptic plasticity, and occurs via N-methyl-D-aspartate type glutamate receptor (NMDAR or GluN) dependent and independent mechanisms. In particular, NMDARs are a major target of alcohol, and are implicated in different types of learning and memory. Therefore, understanding the effect of alcohol on synaptic plasticity and transmission mediated by glutamatergic signaling is becoming important, and this will help us understand the significant contribution of the glutamatergic system in AUD. In the first part of this review, we will briefly discuss the mechanisms underlying long term synaptic plasticity in the dorsal striatum, neocortex and the hippocampus. In the second part we will discuss how alcohol (ethanol, EtOH) can modulate long term synaptic plasticity in these three brain regions, mainly from neurophysiological and electrophysiological studies. Taken together, understanding the mechanism(s) underlying alcohol induced changes in brain function may lead to the development of more effective therapeutic agents to reduce AUDs.