Memory retrieval-induced activation of adult-born neurons generated in response to damage to the dentate gyrus
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The dentate gyrus (DG) is a neurogenic structure that exhibits functional and structural reorganization after injury. Neurogenesis and functional recovery occur after brain damage, and the possible relation between both processes is a matter of study. We explored whether neurogenesis and the activation of new neurons correlated with DG recovery over time. We induced a DG lesion in young adult rats through the intrahippocampal injection of kainic acid and analyzed functional recovery and the activation of new neurons after animals performed a contextual fear memory task (CFM) or a control spatial exploratory task. We analyzed the number of BrdU+ cells that co-localized with doublecortin (DCX) or with NeuN within the damaged DG and evaluated the number of cells in each population that were labelled with the activity marker c-fos after either task. At 10 days post-lesion (dpl), a region of the granular cell layer was devoid of cells, evidencing the damaged area, whereas at 30 dpl this region was significantly smaller. At 10 dpl, the number of BrdU+/DCX+/c-fos positive cells was increased compared to the sham-lesion group, but CFM was impaired. At 30 dpl, a significantly greater number of BrdU+/NeuN+/c-fos positive cells was observed than at 10 dpl, and activation correlated with CFM recovery. Performance in the spatial exploratory task induced marginal c-fos immunoreactivity in the BrdU+/NeuN+ population. We demonstrate that neurons born after the DG was damaged survive and are activated in a time- and task-dependent manner and that activation of new neurons occurs along functional recovery.
KeywordsPlasticity Kainic acid Adult-born neurons activation Hippocampus Injury Cognitive demand IEG Hilus
This work was supported by Grants from Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT) 203015 and Consejo Nacional de Ciencia y Tecnología (CONACyT) 176589. Aguilar-Arredondo is a doctoral student from Programa de Doctorado en Ciencias Biomédicas, Universidad Nacional Autónoma de México (UNAM) and was supported by CONACYT 270435. We thank Clorinda Arias for providing helpful comments on the manuscript and Josué Ramirez Jarquín, Miguel Tapia and Patricia Ferrera for providing technical support.
Compliance with ethical standards
This work has not been published previously, nor is it under review in any other journal. All authors of the study accept the contents of the manuscript and consent to the submission of the work. None of the authors have been cited for any scientific misconduct.
Conflict of interest
The authors have no conflicts of interest to declare.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
Human and animal rights statement
All procedures involving animals were performed in accordance with the ethical standards of the institution or practice at which the studies were conducted.
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