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重复的皮层-状体刺激会产生持续的强迫症类行为
Susanne E Ahmari1, Timothy Spellman, Neria L Douglass
1Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. sea2103@columbia.edu
概括
在小鼠中,对皮质-状-甲状腺-皮质 (CSTC) 电路的重复光遗传刺激诱导了持续的理行为,模仿强迫症 (OCD) 症状. 这种电路过活性的反转是通过fluoxetine治疗.
科学领域:
- 神经科学是一个神经科学.
- 精神病学是一个精神病学.
- 计算神经科学是一种神经科学.
背景情况:
- 皮质 - 条状 - thalamo - 皮质 (CSTC) 电路失调与强迫症 (OCD) 有关.
- 在人类中,CSTC过度活跃和强迫症之间的直接因果关系无法从伦理上进行测试.
研究的目的:
- 调查CSTC电路过度激活在强迫症相关的重复行为发展中的因果作用.
- 探索重复模拟的CSTC过度激活对小鼠模型行为和神经活动的影响.
主要方法:
- 在小鼠中利用光遗传学反复刺激轨道前皮层 (OFC) - 腹中条体 (VMS) 途径,模拟CSTC过度激活.
- 监测行为变化,特别是理频率,并在VMS中记录光唤起的神经元发射.
- 给慢性用fluoxetine,一种标准的强迫症治疗,以评估其对行为和神经活动的影响.
主要成果:
- 急性OFC-VMS刺激没有诱导重复行为.
- 在多天内每天重复刺激逐渐增加了理行为,这种行为在刺激后持续了两周.
- 这种持续的理与后突触VMS神经元中光唤起的发射增加有关.
- 慢性素治疗逆转了增加的理和增强的VMS神经元发射.
结论:
- 不正常的CSTC电路活动的短暂,重复的发作可以建立类似于强迫症的持续行为变化.
- 这项研究提供了一个潜在的因果机制,将CSTC电路功能障碍与持久性精神病理的发展联系起来.
- 这些发现支持fluoxetine在调节强迫症的电路活动和相关行为方面的治疗疗效.
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