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Alcohol. 2019 Dec 16. pii: S0741-8329(19)30280-0. doi: 10.1016/j.alcohol.2019.12.001. [Epub ahead of print]

In Vivo Two-Photon Imaging of Neuronal and Brain Vascular Responses in Mice Chronically Exposed to Ethanol.

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Dept. of Physiology, Augusta University Augusta, GA. Electronic address:
Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425.
Seattle Children's Research Institute, Dept. of Pediatrics, University of Washington, Seattle, WA. Electronic address:
Dept. of Neuroscience, University of Minnesota, Minneapolis, MN. Electronic address:
Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425. Electronic address:


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 4 weekly cycles of chronic intermittent ethanol (CIE) exposure while control mice were exposed to air. After withdrawal (> 72 hr), 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.


arteriole; barrel cortex; neurovascular coupling; orientation selectivity; sensory-evoked dilation; visual cortex

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