腹腔海马体输入到内膜皮层是必要的治疗效果的灭绝在压力大鼠的效果
Denisse Paredes1, David A Morilak1,2
1Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
The international journal of neuropsychopharmacology
|July 22, 2023
概括
恐惧灭绝疗法通过激活大脑衍生神经营养因子 (BDNF) 信号来逆转压力诱导的认知缺陷. 这个过程需要腹部海马体输入到中部前额叶皮层 (mPFC) 以获得治疗效果.
科学领域:
- 神经科学是一个神经科学.
- 认知科学 认知科学
- 精神病学是一个精神病学.
背景情况:
- 创伤后应激障碍 (PTSD) 与认知灵活性缺陷有关,通常涉及中间前额叶皮层 (mPFC).
- 暴露疗法,类似于对动物的恐惧灭绝,有效地扭转了这些缺陷.
- 脑衍生神经营养因子 (BDNF) 在下极膜皮层 (IL) 中的信号传递对于灭绝的治疗效果至关重要,但潜在的电路机制尚不清楚.
研究的目的:
- 调查腹部海马体 (vHipp) 向IL投射的作用,以调解灭绝的认知益处.
- 确定vHipp-IL通路激活和BDNF信号是否对于逆转压力诱导的认知障碍至关重要.
主要方法:
- 在灭绝训练之前,使用设计器受体被设计器药物 (DREADD) 技术独家激活 (DREADD) 技术对IL的vHipp输入进行沉默.
- 使用DREADD激活vHipp向IL的投影,并通过抗体输液评估BDNF信号阻断的影响.
- 在老鼠中使用注意力设置转移测试 (AST) 评估认知灵活性.
主要成果:
- 抑制vHipp输入到IL取消了通常在灭绝后看到的认知改善.
- 直接激活vHipp输入到IL,独立于灭绝,扭转了设置转移中的压力诱导的缺陷.
- 激活vHipp的治疗效果被一种向IL注入的抗BDNF抗体所阻断.
结论:
- 腹腔海马体 (vHipp) 到下边皮层 (IL) 路径的激活对于恐惧灭绝恢复认知灵活性的能力至关重要.
- 由vHipp输入驱动的IL内的BDNF信号传递对于抵消慢性压力诱导的认知缺陷至关重要.
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