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In vivo two-photon imaging of neuronal and brain vascular responses in mice chronically exposed to ethanol.
Alcohol ( IF 2.5 ) Pub Date : 2019-12-17 , DOI: 10.1016/j.alcohol.2019.12.001
Phillip O'Herron 1 , Phillip M Summers 2 , Andy Y Shih 3 , Prakash Kara 4 , John J Woodward 2
Affiliation  

The effects of ethanol on brain function have been extensively studied using a variety of in vitro and in vivo techniques. For example, electrophysiological studies using brain slices from rodents and non-human primates have demonstrated that acute and chronic exposure to ethanol alters the intrinsic excitability and synaptic signaling of neurons within cortical and sub-cortical areas of the brain. In humans, neuroimaging studies reveal alterations in measures of brain activation and connectivity in subjects with alcohol use disorder. While complementary, these methods are inherently limited due to issues related to either disruption of normal sensory input (in vitro slice studies) or resolution (whole brain imaging). In the present study, we used 2-photon laser scanning microscopy in intact animals to assess the impact of chronic ethanol exposure on sensory-evoked neuronal and vascular responses. Adult male C57BL/6J mice were exposed to four weekly cycles of chronic intermittent ethanol (CIE) exposure, while control mice were exposed to air. After withdrawal (≥72 h), a cranial window was placed over the primary visual cortex (V1), and sensory-evoked responses were monitored using the calcium indicator OGB-1. CIE exposure produced small but significant changes in response amplitude (decrease) and orientation selectivity of V1 neurons (increase). While arteriole diameter did not differ between control and CIE mice under baseline conditions, sensory-evoked dilation was enhanced in vessels from CIE-exposed mice as compared to controls. This was accompanied by a reduced latency in response to stimulation. In separate experiments, pial arteriole diameter was measured in the barrel cortex of control and CIE-exposed mice. Baseline diameter of barrel cortex arterioles was similar between control and CIE-exposed mice, but unlike vessels in V1, sensory-evoked dilation of barrel cortex arterioles was similar between the two groups. Together, the results of these studies suggest that chronic exposure to alcohol induces changes in neurovascular coupling that are region-dependent.

中文翻译:


长期暴露于乙醇的小鼠神经元和脑血管反应的体内双光子成像。



乙醇对脑功能的影响已使用各种体外和体内技术进行了广泛研究。例如,使用啮齿动物和非人类灵长类动物脑切片进行的电生理学研究表明,急性和慢性接触乙醇会改变大脑皮质和皮质下区域神经元的内在兴奋性和突触信号传导。在人类中,神经影像学研究揭示了酒精使用障碍患者的大脑激活和连接测量的变化。虽然是互补的,但由于与正常感觉输入(体外切片研究)或分辨率(全脑成像)中断相关的问题,这些方法本质上受到限制。在本研究中,我们在完整动物中使用 2 光子激光扫描显微镜来评估慢性乙醇暴露对感觉诱发的神经元和血管反应的影响。成年雄性 C57BL/6J 小鼠每周接受四个周期的慢性间歇性乙醇 (CIE) 暴露,而对照小鼠则暴露于空气中。停药后(≥72小时),将颅窗放置在初级视觉皮层(V1)上,并使用钙指示剂OGB-1监测感觉诱发反应。 CIE 暴露对 V1 神经元的反应幅度(降低)和方向选择性(增加)产生微小但显着的变化。虽然在基线条件下对照组和 CIE 小鼠的小动脉直径没有差异,但与对照组相比,CIE 暴露小鼠的血管感觉诱发的扩张增强。这伴随着对刺激的反应潜伏期的缩短。在单独的实验中,测量了对照小鼠和 CIE 暴露小鼠的桶状皮质中的软脑膜小动脉直径。 对照组和 CIE 暴露小鼠之间的桶状皮层小动脉的基线直径相似,但与 V1 中的血管不同,两组之间感觉诱发的桶状皮层小动脉扩张相似。总之,这些研究的结果表明,长期接触酒精会引起区域依赖性神经血管耦合的变化。
更新日期:2020-04-20
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