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在成模型中,静态突触可塑性是强迫性的基础
Vincent Pascoli1, Agnès Hiver1, Ruud Van Zessen1
1Department of Basic Neurosciences, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Nature
|December 21, 2018
概括
强迫性寻找药物是一种成的标志, 这种突触增强是持续使用有害物质的基础,
科学领域:
- 神经科学
- 关于成的研究
- 行为科学
背景情况:
- 半边缘多巴胺系统强化行为, 但慢性过度刺激, 如药物滥用,
- 了解驱动强迫性寻找药物的神经机制对于开发有效的成治疗至关重要.
研究的目的:
- 在小鼠模型中研究强迫强化的神经回路.
- 鉴定特定的大脑区域和与持续寻找毒品行为相关的突触变化.
主要方法:
- 允许小鼠以光遗传方式自我刺激多巴胺神经元,其中一些受到惩罚 (电击).
- 监测了轨道前皮层 (OFC) 到背上条纹体投射的活性.
- 在此途径中的突触可塑性 (增强和减弱) 被操纵以评估其在强迫行为中的因果作用.
主要成果:
- 强迫性杆按压, 表明类似成的行为, 与OFC增强的活动相关.
- 在表现强迫行为的小鼠中观察到OFC-striatal通道的永久性突触强化.
- 在体内对这种突触增强的操纵导致了强迫性的杆压力,而减强则逆转了这种情况.
结论:
- 突触强化是强迫性强化的一个关键驱动器.
- 这一发现提供了一个特定的突触机制,
- 针对OFC-状突触可塑性可能为成提供一种新的治疗策略.
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