长期暴露于乙醇会导致RMTg投射mPFC神经元的长期,分区域特定的生理适应
Kathryn R Przybysz1, Joel E Shillinglaw1, Shannon R Wheeler1
1Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois Chicago, Chicago, IL, USA.
Neuropharmacology
|August 8, 2024
概括
长期暴露于乙醇会改变大脑电路,特别是影响下边缘介质前额叶皮层 (mPFC) 投射到面向介质质核 (RMTg),可能会影响酒精使用障碍的恢复.
科学领域:
- 神经科学是一个神经科学.
- 成的神经生物学成的神经生物学
- 酒精使用障碍的电路
背景情况:
- 长期暴露于乙醇会诱导中枢前额叶皮层 (mPFC) 的神经适应,导致适应不良的行为,并阻碍酒精使用障碍 (AUD) 的恢复.
- 虽然皮层-亚皮层电路扮演着不同的行为角色,但慢性乙醇对这些路径的特定生理影响仍未得到充分探索.
- 脊椎中介质核 (RMTg) 显示慢性乙醇的功能改变,其从mPFC的输入是研究的关键领域.
研究的目的:
- 研究慢性乙醇暴露对投射到RMTg的特定mPFC神经元群体的生理后果.
- 为了区分慢性乙醇对前临界 (PL) 和下临界 (IL) mPFC电路的影响,针对RMTg.
- 为了阐明慢性乙醇暴露后mPFC中电路特定的神经适应.
主要方法:
- 在成年雄性Long-Evans老鼠中使用了慢性间歇性乙醇 (CIE) 蒸汽暴露范式.
- 向RMTg注入光反射线,以识别向该核投射的mPFC神经元.
- 在RMTg投射和投射未定义的5层金字塔神经元上进行全细胞补丁电生理学,在乙醇暴露后7-10天.
主要成果:
- 在RMTg投射IL神经元中,CIE暴露显著增加了内在刺激能力和自发刺激/抑制后突触电流 (sEPSC/IPSC).
- 在投射RMTg的PL神经元中没有观察到持久的刺激性变化;然而,投射未定义的PL神经元在CIE后显示出刺激性降低.
- 在RMTg投射PL神经元中,CIE暴露增加了SEPSC的频率.
结论:
- 长期暴露于乙醇会在mPFC中诱导独特的,分区域和电路特定的神经适应.
- 阴下 (IL) mPFC 到 RMTg 的投射表现出在慢性乙醇暴露后对长期生理变化的独特脆弱性.
- 这些发现凸显了IL mPFC-RMTg通路作为减轻与酒精有关的行为潜在的治疗点.
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