Abstinence after alcohol dependence leads to structural and functional recovery in many regions of the brain, especially the hippocampus. Significant increases in neural stem cell (NSC) proliferation and subsequent “reactive neurogenesis” coincides with structural recovery in hippocampal dentate gyrus (DG). However, whether these reactively born neurons are integrated appropriately into neural circuits remains unknown. Therefore, adult male rats were exposed to a binge model of alcohol dependence. On day 7 of abstinence, the peak of reactive NSC proliferation, rats were injected with bromodeoxyuridine (BrdU) to label dividing cells. After six weeks, rats underwent Morris Water Maze (MWM) training then were sacrificed ninety minutes after the final training session. Using fluorescent immunohistochemistry for c-Fos (neuronal activation), BrdU, and Neuronal Nuclei (NeuN), we investigated whether neurons born during reactive neurogenesis were incorporated into a newly learned MWM neuronal ensemble. Prior alcohol exposure increased the number of BrdU+ cells and newborn neurons (BrdU+/NeuN+ cells) in the DG versus controls. However, prior ethanol exposure had no significant impact on MWM-induced c-Fos expression. Despite increased BrdU+ neurons, no difference in the number of activated newborn neurons (BrdU+/c-Fos+/NeuN+) was observed. These data suggest that neurons born during alcohol-induced reactive neurogenesis are functionally integrated into hippocampal circuitry.
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This research was funded by NIH grants R01AA016959 (KN), R01 AA025591 (KN), F31AA023459 (CGN), T32AA007471 and the University of Kentucky Department of Pharmaceutical Sciences.
The datasets generated for this study are included in the article. Further inquiries can be directed to the corresponding author.
Nawarawong, Natalie N.; Nickell, Chelsea G.; Hopkins, Deann M.; Pauly, James R.; and Nixon, Kimberly, "Functional Activation of Newborn Neurons Following Alcohol-Induced Reactive Neurogenesis" (2021). Pharmaceutical Sciences Faculty Publications. 163.