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首页> 外文期刊>The European Journal of Neuroscience >Molecular mechanisms underlying striatal synaptic plasticity: relevance to chronic alcohol consumption and seeking
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Molecular mechanisms underlying striatal synaptic plasticity: relevance to chronic alcohol consumption and seeking

机译：纹状体突触塑性的分子机制：与慢性酒精消费的相关性和寻求的相关性

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Abstract The striatum, the input structure of the basal ganglia, is a major site of learning and memory for goal‐directed actions and habit formation. Spiny projection neurons of the striatum integrate cortical, thalamic, and nigral inputs to learn associations, with cortico‐striatal synaptic plasticity as a learning mechanism. Signaling molecules implicated in synaptic plasticity are altered in alcohol withdrawal, which may contribute to overly strong learning and increased alcohol seeking and consumption. To understand how interactions among signaling molecules produce synaptic plasticity, we implemented a mechanistic model of signaling pathways activated by dopamine D1 receptors, acetylcholine receptors, and glutamate. We use our novel, computationally efficient simulator, NeuroRD, to simulate stochastic interactions both within and between dendritic spines. Dopamine release during theta burst and 20‐Hz stimulation was extrapolated from fast‐scan cyclic voltammetry data collected in mouse striatal slices. Our results show that the combined activity of several key plasticity molecules correctly predicts the occurrence of either LTP, LTD, or no plasticity for numerous experimental protocols. To investigate spatial interactions, we stimulate two spines, either adjacent or separated on a 20‐μm dendritic segment. Our results show that molecules underlying LTP exhibit spatial specificity, whereas 2‐arachidonoylglycerol exhibits a spatially diffuse elevation. We also implement changes in NMDA receptors, adenylyl cyclase, and G protein signaling that have been measured following chronic alcohol treatment. Simulations under these conditions suggest that the molecular changes can predict changes in synaptic plasticity, thereby accounting for some aspects of alcohol use disorder.
机译：摘要纹章，基底神经节的输入结构，是目标导向行动和习惯形成的主要学习和记忆的主要站点。纹状体的多刺投影神经元整合皮质，丘脑和核心投入来学习关联，皮质纹突触可塑性作为学习机制。涉及突触塑性的信号分子在酒精戒断中改变，这可能导致过度强大的学习和增加酒精寻求和消费。为了了解信令分子之间的相互作用产生突触可塑性，我们实施了由多巴胺D1受体，乙酰胆碱受体和谷氨酸活化的信号传导途径的机械模型。我们使用我们的新颖，计算上高效的模拟器Neurord，模拟树突刺之间和之间的随机相互作用。在小鼠纹状体切片中收集的快速扫描循环伏安法数据外推开θ爆发和20 hz刺激期间的多巴胺释放。我们的研究结果表明，几个关键塑性分子的组合活动正确预测了LTP，LTD，LTD，无论多种实验方案的可塑性。为了研究空间相互作用，我们刺激两个刺，邻近或分离在20μm树枝状段。我们的结果表明，LTP的底层分子表现出空间特异性，而2-arachidonoylglycerol在空间上漫射升高。我们还在慢性醇处理后测量的NMDA受体，腺苷酸环酶和G蛋白信号传导的变化。这些条件下的模拟表明分子变化可以预测突触可塑性的变化，从而占酒精使用障碍的某些方面。

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