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Functional recovery of the dentate gyrus after a focal lesion is accompanied by structural reorganization in the adult rat

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Abstract

The adult brain is highly plastic and tends to undergo substantial reorganization after injury to compensate for the lesion effects. It has been shown that such reorganization mainly relies on anatomical and biochemical modifications of the remaining cells which give rise to a network rewiring without reinstating the original morphology of the damaged region. However, few studies have analyzed the neurorepair potential of a neurogenic structure. Thus, the aim of this work was to analyze if the DG could restore its original morphology after a lesion and to establish if the structural reorganization is accompanied by behavioral and electrophysiological recovery. Using a subepileptogenic injection of kainic acid (KA), we induced a focal lesion in the DG and assessed in time (1) the loss and recovery of dependent and non dependent DG cognitive functions, (2) the anatomical reorganization of the DG using a stereological probe and immunohistochemical markers for different neuronal maturation stages and, (3) synaptic plasticity as assessed through the induction of in vivo long-term potentiation (LTP) in the mossy fiber pathway (CA3-DG). Our results show that a DG focal lesion with KA leads to a well delimited region of neuronal loss, disorganization of the structure, the loss of associated mnemonic functions and the impairment to elicit LTP. However, behavioral and synaptic plasticity expression occurs in a time dependent fashion and occurs along the morphological restoration of the DG. These results provide novel information on neural plasticity events associated to functional reorganization after damage.

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Acknowledgments

We thank Pedro Medina, Miguel Tapia, Patricia Ferrera and Alicia Sampieri for technical assistance. We thank Verdon Taylor for providing facilities in the development of histochemical procedures. This project was supported by DGAPA-PAPIIT IN215609, IN213210 and CONACyT 60851.

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  1. Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, AP 70-228, 04510, México, D.F., México

    Angélica Zepeda, Andrea Aguilar-Arredondo, Gabriela Michel & Clorinda Arias

  2. División de Investigación y Estudios de Posgrado, Facultad de Psicología, Universidad Nacional Autónoma de México, 04510, México, D.F., México

    Angélica Zepeda, Laura Elisa Ramos-Languren & Martha L. Escobar

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  1. Angélica Zepeda
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  2. Andrea Aguilar-Arredondo
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  3. Gabriela Michel
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  4. Laura Elisa Ramos-Languren
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Correspondence to Angélica Zepeda.

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Zepeda, A., Aguilar-Arredondo, A., Michel, G. et al. Functional recovery of the dentate gyrus after a focal lesion is accompanied by structural reorganization in the adult rat. Brain Struct Funct 218, 437–453 (2013). https://doi.org/10.1007/s00429-012-0407-4

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