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.
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 and 270435.
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.
- Besnard A, Serge L, Jocelyne C (2014) Comparative dynamics of MAPK/ERK signalling components and immediate early genes in the hippocampus and amygdala following contextual fear conditioning and retrieval. Brain Struct Funct 219:415–430. https://doi.org/10.1007/s00429-013-0505-y CrossRefPubMedGoogle Scholar
- Kawai T, Takagi N, Miyake-Takagi K et al (2004) Characterization of BrdU-positive neurons induced by transient global ischemia in adult hippocampus. J Cereb Blood Flow Metab 24:548–555. https://doi.org/10.1097/01.WCB.0000117807.29980.1A CrossRefPubMedGoogle Scholar
- Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Elsevier, New YorkGoogle Scholar
- Platschek S, Cuntz H, Deller T, Jedlicka P (2017) Lesion-induced dendritic remodeling as a new mechanism of homeostatic structural plasticity in the adult brain. In: Van Ooyen A, Butz-Ostendorf M (eds) The rewiring brain: a computational approach to structural plasticity in the adult brain. Academic Press, San Diego, pp 203–218CrossRefGoogle Scholar
- Snyder JS, Hong NS, McDonald RJ, Wojtowicz JM (2005) A role for adult neurogenesis in spatial long-term memory. Neuroscience 130:843–852. https://doi.org/10.1016/j.neuroscience.2004.10.009 CrossRefPubMedGoogle Scholar
- Suh H, Deng W, Gage FH (2009) Signaling in adult neurogenesis. Annu Rev Cell Dev Biol 25:253–275. https://doi.org/10.1146/annurev.cellbio.042308.113256 CrossRefPubMedGoogle Scholar
- Sun D, Daniels TE, Rolfe A et al (2015) Inhibition of injury-induced cell proliferation in the dentate gyrus of the hippocampus impairs spontaneous cognitive recovery after traumatic brain injury. J Neurotrauma 32:495–505. https://doi.org/10.1089/neu.2014.3545 CrossRefPubMedPubMedCentralGoogle Scholar
- Varela-Nallar L, Rojas-Abalos M, Abbott AC et al (2014) Chronic hypoxia induces the activation of the Wnt/β-catenin signaling pathway and stimulates hippocampal neurogenesis in wild-type and APPswe-PS1∆E9 transgenic mice in vivo. Front Cell Neurosci. https://doi.org/10.3389/fncel.2014.00017 CrossRefPubMedPubMedCentralGoogle Scholar
- Zepeda A, Sengpiel F, Guagnelli MA, Vaca L, Arias C (2004) Functional reorganization of visual cortex maps after ischemic lesions is accompanied by changes in expression of cytoskeletal proteins and NMDA and GABA(A) receptor subunits. J Neurosci 24(8):1812–1821. https://doi.org/10.1523/JNEUROSCI.3213-03.2004 CrossRefPubMedGoogle Scholar