Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157.
Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157
eNeuro. 2020 Mar 6;7(2). doi: 10.1523/ENEURO.0132-19.2019. Print 2020 Mar/Apr.
The medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) have strong reciprocal connectivity. Projections from the BLA to the mPFC can drive innate, anxiety-related behaviors, but it is unclear whether reciprocal projections from the mPFC to BLA have similar roles. Here, we use optogenetics and chemogenetics to characterize the neurophysiological and behavioral alterations produced by chronic ethanol exposure and withdrawal on dorsal mPFC (dmPFC) and ventral mPFC (vmPFC) medial prefrontal cortical terminals in the BLA. We exposed adult male Sprague Dawley rats to chronic intermittent ethanol (CIE) using vapor chambers, measured anxiety-like behavior on the elevated zero maze, and used electrophysiology to record glutamatergic and GABAergic responses in BLA principal neurons. We found that withdrawal from a 7 d CIE exposure produced opposing effects at dmPFC (increased glutamate release) and vmPFC (decreased glutamate release) terminals in the BLA. Chemogenetic inhibition of dmPFC terminals in the BLA attenuated the increased anxiety-like behavior we observed during withdrawal. These data demonstrate that chronic ethanol exposure and withdrawal strengthen the synaptic connections between the dmPFC and BLA but weakens the vmPFC-BLA pathway. Moreover, facilitation of the dmPFC-BLA pathway during withdrawal contributes to anxiety-like behavior. Given the opposing roles of dmPFC-BLA and vmPFC-BLA pathways in fear conditioning, our results suggest that chronic ethanol exposure simultaneously facilitates circuits involved in the acquisition of and diminishes circuits involved with the extinction of withdrawal-related aversive behaviors.
内侧前额叶皮层（mPFC）和基底外侧杏仁核（BLA）之间具有强烈的相互连接。BLA 投射到 mPFC 的投射可以驱动先天的、与焦虑相关的行为，但尚不清楚 mPFC 到 BLA 的相互投射是否具有类似的作用。在这里，我们使用光遗传学和化学遗传学来描述慢性乙醇暴露和戒断对 BLA 中背侧 mPFC（dmPFC）和腹侧 mPFC（vmPFC）内侧前额叶皮质末端的神经生理和行为改变。我们使用蒸气室使成年雄性 Sprague Dawley 大鼠暴露于慢性间歇性乙醇（CIE），在高架零迷宫上测量焦虑样行为，并使用电生理学记录 BLA 主神经元中的谷氨酸能和 GABA 能反应。我们发现，从 7 天的 CIE 暴露中戒断会对 BLA 中的 dmPFC（谷氨酸释放增加）和 vmPFC（谷氨酸释放减少）末端产生相反的影响。BLA 中的 dmPFC 末端的化学遗传抑制减弱了我们在戒断期间观察到的增加的焦虑样行为。这些数据表明，慢性乙醇暴露和戒断增强了 dmPFC 和 BLA 之间的突触连接，但削弱了 vmPFC-BLA 通路。此外，戒断期间 dmPFC-BLA 通路的易化有助于焦虑样行为。鉴于 dmPFC-BLA 和 vmPFC-BLA 通路在恐惧条件反射中具有相反的作用，我们的结果表明，慢性乙醇暴露同时促进了与获得相关的回路的激活，并减弱了与戒断相关的厌恶行为的消退相关的回路。
