慢性乙醇暴露对接受眶额皮质和杏仁核基底外侧趋同输入的背内侧纹状体神经元的影响。

IF 4.6 2区 医学 Q1 NEUROSCIENCES Neuropharmacology Pub Date : 2025-01-13 DOI:10.1016/j.neuropharm.2025.110303
Sudarat Nimitvilai-Roberts , Marcelo F. Lopez , John J. Woodward
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引用次数: 0

摘要

酒精使用障碍与皮质-杏仁核-纹状体回路的功能改变有关,如眶额皮质(OFC)、基底外侧杏仁核(BLA)及其与背内侧纹状体(DMS)的连接被证明与目标导向行为有关。通过反向追踪,我们之前报道了在慢性间歇乙醇(CIE)暴露3- 7天后小鼠dms -投射OFC神经元的兴奋性增强。在同样的动物中,dms -突出的BLA神经元的尖峰在停药后3天减少,随后在7天和14天增加。在当前的研究中,我们使用跨突触标记和切片电生理学来研究CIE暴露对接收OFC和BLA收敛输入的DMS神经元的影响。小鼠OFC (AAV1-Cre)和BLA (AAV1-Flpo)中注入顺行跨突触AAV, DMS中注入Cre-On/Flp-On-YFP AAV,然后进行4周的空气或CIE蒸汽暴露。YFP + DMSOFC-BLA神经元的电流钳记录显示三种不同的放电模式:有规律的尖峰,有规律的尖峰后去极化阻滞,有规律的尖峰,在高电流阶(称为FANS)出现动作电位和平台电位的加宽。在雄性和雌性小鼠中,与空气控制相比,从CIE暴露中退出显着增加了常规尖峰神经元的兴奋性。在fan神经元上观察到更微妙的影响,放电的增加和减少是当前步骤和性别依赖的。这些发现为越来越多的文献提供了证据,证明与强迫/习惯性行为有关的皮质-杏仁核-纹状体回路中的神经元如何受到慢性酒精暴露的影响。
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Effects of chronic ethanol exposure on dorsal medial striatal neurons receiving convergent inputs from the orbitofrontal cortex and basolateral amygdala
Alcohol use disorder is associated with altered function of cortical-amygdala-striatal circuits such as the orbitofrontal cortex (OFC), basolateral amygdala (BLA) and their connections to the dorsal medial striatum (DMS) shown to be involved in goal-directed actions. Using retrobead tracing, we previously reported enhanced excitability of DMS-projecting OFC neurons in mice following 3-to-7-day withdrawal from chronic intermittent ethanol (CIE) exposure. In the same animals, spiking of DMS-projecting BLA neurons was decreased at 3-days post-withdrawal followed by an increase in firing at 7- and 14-days. In the current study, we used transsynaptic labeling and slice electrophysiology to investigate the effects of CIE exposure on DMS neurons that receive convergent inputs from the OFC and BLA. Mice were infused with anterograde transsynaptic AAVs in the OFC (AAV1-Cre) and BLA (AAV1-Flpo) and a Cre-On/Flp-On-YFP AAV in the DMS followed by 4 weekly cycles of Air or CIE vapor exposure. Current-clamp recordings of YFP + DMSOFC−BLA neurons showed three distinct patterns of firing: regular spiking, regular spiking followed by depolarization block and regular spiking with the appearance of broadened action potentials and plateau potentials at higher current steps (termed FANS). In both male and female mice, withdrawal from CIE exposure significantly increased the excitability of regular spiking neurons as compared to air controls. More subtle effects were observed on FANS neurons with both increases and decreases in firing that were current step and sex-dependent. These findings add to a growing literature demonstrating how neurons within cortical-amygdala-striatal circuits implicated in compulsive/habitual behaviors are impacted by chronic alcohol exposure.
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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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