Chronic ethanol exposure produces long-lasting, subregion-specific physiological adaptations in RMTg-projecting mPFC neurons

IF 4.6 2区 医学 Q1 NEUROSCIENCES Neuropharmacology Pub Date : 2024-08-06 DOI:10.1016/j.neuropharm.2024.110098
Kathryn R. Przybysz, Joel E. Shillinglaw, Shannon R. Wheeler, Elizabeth J. Glover
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Abstract

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.

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慢性乙醇暴露会在 RMTg 投射的 mPFC 神经元中产生持久的、亚区域特异性的生理适应。
长期接触乙醇会在内侧前额叶皮层(mPFC)中产生神经适应,从而促进不良行为的发生,影响酒精使用障碍的康复。尽管有证据表明,不同的皮质-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。喙内侧被盖核(RMTg)会因长期接触乙醇而发生功能性改变。我们最近的研究发现了从 mPFC 到 RMTg 的密集输入,但慢性乙醇暴露对该回路的影响尚不清楚。在本研究中,我们检测了慢性乙醇暴露后投射到 RMTg 的前边缘(PL)和下边缘(IL)mPFC 神经元的生理变化。我们向成年雄性 Long-Evans 大鼠的 RMTg 注射了荧光反向珠,并使用为期 14 天的慢性间歇性乙醇(CIE)蒸汽暴露范例使其产生依赖性。乙醇暴露7-10天后,对荧光标记(RMTg投射)和未标记(未定义投射)的第5层锥体神经元进行全细胞膜片钳电生理记录。在RMTg投射的IL神经元中,CIE暴露明显增加了其内在兴奋性以及自发兴奋性和抑制性突触后电流(sE/IPSCs)。相比之下,在RMTg投射的PL神经元中没有观察到兴奋性的持久变化,尽管在投射未定义的PL神经元中观察到了CIE诱导的兴奋性降低。CIE暴露还增加了RMTg投射的PL神经元的sEPSCs频率。这些数据揭示了慢性乙醇暴露后 mPFC 中新的亚区域和回路特异性神经适应,并揭示了 IL mPFC-RMTg 投射在慢性乙醇暴露的长期影响下具有独特的脆弱性。
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来源期刊
Neuropharmacology
Neuropharmacology 医学-神经科学
CiteScore
10.00
自引率
4.30%
发文量
288
审稿时长
45 days
期刊介绍: Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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