title: Heterogeneous integration of adult-generated granule cells into the epileptic brain.
abstract: The functional impact of adult-generated granule cells in the epileptic brain is unclear, with data supporting both protective and maladaptive roles. These conflicting findings could be explained if new granule cells integrate heterogeneously, with some cells taking neutral or adaptive roles and others contributing to recurrent circuitry supporting seizures. Here, we tested this hypothesis by completing detailed morphological characterizations of age- and experience-defined cohorts of adult-generated granule cells from transgenic mice. The majority of newborn cells exposed to an epileptogenic insult exhibited reductions in dendritic spine number, suggesting reduced excitatory input to these cells. A significant subset, however, exhibited higher spine numbers. These latter cells tended to have enlarged cell bodies, long basal dendrites, or both. Moreover, cells with basal dendrites received significantly more recurrent mossy fiber input through their apical dendrites, indicating that these cells are robustly integrated into the pathological circuitry of the epileptic brain. These data imply that newborn cells play complex--and potentially conflicting--roles in epilepsy.
authors.affiliation: Department of Anesthesia, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Murphy
authors.forename: Raymund Y K
authors.initials: RY
authors.lastname: Pun
authors.forename: Hulian
authors.initials: H
authors.lastname: Yin
authors.forename: Christian R
authors.initials: CR
authors.lastname: Faulkner
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Loepke
authors.forename: Steve C
authors.initials: SC
authors.lastname: Danzer
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D027682:Cation Transport Proteins / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D003712:Dendrites / Q000473:pathology* / Q000648:ultrastructure; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D021621:Imaging, Three-Dimensional; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal / Q000379:methods; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000473:pathology*; D010862:Pilocarpine / Q000009:adverse effects; D018709:Statistics, Nonparametric; D013226:Status Epilepticus / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D018800:Thy-1 Antigens / Q000235:genetics; D000071676:Zinc Finger Protein GLI1
chemical_list: D027682:Cation Transport Proteins; C498520:Gli1 protein, mouse; D051741:Kruppel-Like Transcription Factors; C498426:Slc39a3 protein, mouse; D018800:Thy-1 Antigens; D000071676:Zinc Finger Protein GLI1; D010862:Pilocarpine; D049452:Green Fluorescent Proteins