title: Axonal plasticity of age-defined dentate granule cells in a rat model of mesial temporal lobe epilepsy.
abstract: Dentate granule cell (DGC) mossy fiber sprouting (MFS) in mesial temporal lobe epilepsy (mTLE) is thought to underlie the creation of aberrant circuitry which promotes the generation or spread of spontaneous seizure activity. Understanding the extent to which populations of DGCs participate in this circuitry could help determine how it develops and potentially identify therapeutic targets for regulating aberrant network activity. In this study, we investigated how DGC birthdate influences participation in MFS and other aspects of axonal plasticity using the rat pilocarpine-induced status epilepticus (SE) model of mTLE. We injected a retrovirus (RV) carrying a synaptophysin-yellow fluorescent protein (syp-YFP) fusion construct to birthdate DGCs and brightly label their axon terminals, and compared DGCs born during the neonatal period with those generated in adulthood. We found that both neonatal and adult-born DGC populations participate, to a similar extent, in SE-induced MFS within the dentate gyrus inner molecular layer (IML). SE did not alter hilar MF bouton density compared to sham-treated controls, but adult-born DGC bouton density was greater in the IML than in the hilus after SE. Interestingly, we also observed MF axonal reorganization in area CA2 in epileptic rats, and these changes arose from DGCs generated both neonatally and in adulthood. These data indicate that both neonatal and adult-generated DGCs contribute to axonal reorganization in the rat pilocarpine mTLE model, and indicate a more complex relationship between DGC age and participation in seizure-related plasticity than was previously thought.
authors.affiliation: Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, United States; Department of Neurology, University of Michigan Medical Center, Ann Arbor, MI, United States.
authors.forename: A L
authors.initials: AL
authors.lastname: Althaus
authors.affiliation: Department of Neurology, University of Michigan Medical Center, Ann Arbor, MI, United States; VA Ann Arbor Healthcare System, Ann Arbor, MI, United States.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI, United States; Department of Neurology, University of Michigan Medical Center, Ann Arbor, MI, United States; VA Ann Arbor Healthcare System, Ann Arbor, MI, United States. Electronic address: parent@umich.edu.
authors.forename: J M
authors.initials: JM
authors.lastname: Parent
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000473:pathology / Q000502:physiology*; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology*; D009473:Neuronal Plasticity; D010862:Pilocarpine; D017966:Pyramidal Cells / Q000473:pathology / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology
chemical_list: D010862:Pilocarpine
keywords: Axonal reorganization; Mossy fiber sprouting; Neural stem cell.; Neurogenesis; Seizure