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基底前脑-侧面 habenula 输入和控制冲动行为
Eun-Kyung Hwang1,2, Agustin Zapata1, Vivian Hu1
1Computational and Systems Neuroscience Branch, Electrophysiology Research Section, U.S. Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, 21224, USA.
概括
冲动控制缺陷与神经认知障碍有关. 这项研究揭示了一条大麻素调节的通往侧面大脑 (LHb) 的途径,该途径影响大鼠的冲动行为,从而确定了一个潜在的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 行为神经科学 行为神经科学
- 神经药理学神经药理学
背景情况:
- 冲动控制缺陷是注意力缺陷多动障碍 (ADHD),物质使用障碍 (SUD) 和创伤性脑损伤 (TBI) 的特征.
- 侧面囊 (LHb) 在调节冲动性方面发挥着至关重要的作用,其完整的功能是必要的,以限制冲动性行为.
- 了解冲动性背后的特定大脑电路和机制对于开发有效的治疗干预至关重要.
研究的目的:
- 调查突触输入到LHb参与调节反应抑制和冲动行为.
- 阐明神经化学和电路层面的机制,特别是涉及大麻素信号的机制,调节与冲动控制相关的LHb功能.
主要方法:
- 利用逆行式黄金追踪来识别基底前脑 (BF) 输入到LHb,特别是来自腹和核外 (VP/NAcs).
- 采用细胞和电路方法,包括光遗传学,来操纵和评估VP/NAcs输入到LHb的功能.
- 在老鼠身上进行行为实验,以测量反应抑制和冲动性,并检查系统 Δ9 - 四大麻素 (Δ9 -THC) 和 LHb CB1R 反对作用.
主要成果:
- 确定了一条从VP/NAcs到LHb的GABAergic通路,由大麻素CB1受体 (CB1R) 调节,该通路以强力抑制LHb神经元活动.
- 对LHb输入的VP/NAcs光遗传刺激抑制了LHb反应的受损,而这种途径的抑制没有影响冲动控制.
- 在雄性大鼠中,Δ9-THC的全身管理增加了冲动性,这种效果被LHb CB1R对抗阻断,但这并不涉及VP/NAcs通路.
结论:
- 来自VP/NAc的LHb的抑制性附属体,由CB1Rs调节,在调节冲动行为中起作用.
- 德-THC的促冲动效应可能通过LHb中的CB1Rs进行调解,但不仅仅通过已识别的VP/NAcs抑制途径.
- 这项研究发现了一种新型的对大麻素敏感电路,影响着冲动控制,为治疗特征是冲动性的疾病提供了潜在的目标.
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