Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois Chicago, Chicago, IL, USA.
Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois Chicago, Chicago, IL, USA.
Neuropharmacology. 2024 Nov 15;259:110098. doi: 10.1016/j.neuropharm.2024.110098. Epub 2024 Aug 6.
Chronic ethanol exposure produces neuroadaptations in the medial prefrontal cortex (mPFC) that are thought to facilitate maladaptive behaviors that interfere with recovery from alcohol use disorder. Despite evidence that different cortico-subcortical projections play distinct roles in behavior, few studies have examined the physiological effects of chronic ethanol at the circuit level. The rostromedial tegmental nucleus (RMTg) is functionally altered by chronic ethanol exposure. Our recent work identified dense input from the mPFC to the RMTg, yet the effects of chronic ethanol exposure on this circuitry is unknown. In the current study, we examined physiological changes after chronic ethanol exposure in prelimbic (PL) and infralimbic (IL) mPFC neurons projecting to the RMTg. Adult male Long-Evans rats were injected with fluorescent retrobeads into the RMTg and rendered dependent using a 14-day chronic intermittent ethanol (CIE) vapor exposure paradigm. Whole-cell patch-clamp electrophysiological recordings were performed in fluorescently-labeled (RMTg-projecting) and -unlabeled (projection-undefined) layer 5 pyramidal neurons 7-10 days following ethanol exposure. CIE exposure significantly increased intrinsic excitability as well as spontaneous excitatory and inhibitory postsynaptic currents (sE/IPSCs) in RMTg-projecting IL neurons. In contrast, no lasting changes in excitability were observed in RMTg-projecting PL neurons, although a CIE-induced reduction in excitability was observed in projection-undefined PL neurons. CIE exposure also increased the frequency of sEPSCs in RMTg-projecting PL neurons. These data uncover novel subregion- and circuit-specific neuroadaptations in the mPFC following chronic ethanol exposure and reveal that the IL mPFC-RMTg projection is uniquely vulnerable to long-lasting effects of chronic ethanol exposure. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".
慢性乙醇暴露会导致内侧前额叶皮层（mPFC）发生神经适应，这些适应被认为促进了适应不良的行为，从而干扰了酒精使用障碍的恢复。尽管有证据表明不同的皮质下投射在行为中发挥着不同的作用，但很少有研究在回路水平上研究慢性乙醇的生理效应。腹侧被盖区（RMTg）在慢性乙醇暴露后功能发生改变。我们最近的工作发现，mPFC 对 RMTg 的密集输入，但慢性乙醇暴露对该回路的影响尚不清楚。在目前的研究中，我们检查了慢性乙醇暴露后投射到 RMTg 的前额叶皮层（PL）和下前额叶皮层（IL）神经元的生理变化。成年雄性长耳大鼠将荧光逆行示踪剂注射到 RMTg 中，并通过 14 天慢性间歇性乙醇（CIE）蒸气暴露范式使其依赖。在乙醇暴露后 7-10 天，对荧光标记（RMTg 投射）和未标记（无投射）第 5 层锥体神经元进行全细胞膜片钳电生理记录。CIE 暴露显著增加了 RMTg 投射 IL 神经元的固有兴奋性以及自发性兴奋性和抑制性突触后电流（sE/IPSCs）。相比之下，在 RMTg 投射 PL 神经元中没有观察到持久的兴奋性变化，尽管在 RMTg 投射 PL 神经元中观察到 CIE 诱导的兴奋性降低。CIE 暴露还增加了 RMTg 投射 PL 神经元中 sEPSC 的频率。这些数据揭示了慢性乙醇暴露后内侧前额叶皮层的新的亚区和回路特异性神经适应，并表明 IL mPFC-RMTg 投射对慢性乙醇暴露的持久影响特别脆弱。本文是“PFC 回路功能在精神疾病及相关模型中的特刊”的一部分。
