多巴胺能神经元的化学遗传抑制减少了刺激诱导的多巴胺释放,从而改变了前额叶皮层中血液动力学反应的功能
Cornelia Helbing1,2, Marta Brocka2,3, Alberto Arboit1
1Functional Neuroimaging Group, Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Magdeburg, Germany.
内源性多巴胺释放会在不同区域不同影响大脑活动. 抑制多巴胺神经元降低了核中依赖血氧水平 (BOLD) 的反应,但不是中部前额叶皮质.
科学领域:
- 神经科学是一个神经科学.
- 神经成像是一种神经成像.
背景情况:
- 半边缘多巴胺系统在奖励和动机方面发挥着至关重要的作用.
- 了解多巴胺对大脑活动的精确影响对于解释神经成像数据至关重要.
研究的目的:
- 研究内源性释放的多巴胺如何影响通过功能磁共振成像 (fMRI) 测量的刺激诱导的血氧水平依赖 (BOLD) 反应.
主要方法:
- 用于小鼠,其抑制性设计者受体仅由设计药物 (DREADDs) 激活在腹膜区域 (VTA) 神经元中.
- 电刺激的fimbria/fornix诱导多巴胺释放和大胆的信号.
- 克洛扎N-氧化物 (CNO) 激活了DREADDs以抑制多巴胺释放.
- 快速扫描循环电压测量测量了核中的多巴胺释放 (NAcc).
主要成果:
- 在NAcc中,CNO的使用显著降低了多巴胺释放和BOLD反应.
- 中部前额叶皮层 (mPFC) 的BOLD反应没有显著减少,但显示出血液动力学反应向左转移.
- 格兰杰因果关系测试显示,在CNO治疗后,海马体和mPFC中的BOLD信号之间的时间关系发生了变化.
- 没有VTA DREADDs的对照大鼠没有表现出CNO介导的效应.
结论:
- 内源性多巴胺激活对刺激诱导的BOLD反应具有区域特异性影响.
- 没有单一的fMRI参数可以普遍表明多巴胺基系统活性增加.
- 这些发现凸显了解释fMRI信号与多巴胺系统功能相关的复杂性.
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