title: Neural injury alters proliferation and integration of adult-generated neurons in the dentate gyrus.
abstract: Neural plasticity following brain injury illustrates the potential for regeneration in the central nervous system. Lesioning of the perforant path, which innervates the outer two-thirds of the molecular layer of the dentate gyrus, was one of the first models to demonstrate structural plasticity of mature granule cells (Parnavelas et al., 1974; Caceres and Steward, 1983; Diekmann et al., 1996). The dentate gyrus also harbors a continuously proliferating population of neuronal precursors that can integrate into functional circuits and show enhanced short-term plasticity (Schmidt-Hieber et al., 2004; Abrous et al., 2005). To examine the response of adult-generated granule cells to unilateral complete transection of the perforant path in vivo, we tracked these cells using transgenic POMC-EGFP mice or by retroviral expression of GFP. Lesioning triggered a marked proliferation of newborn neurons. Subsequently, the dendrites of newborn neurons showed reduced complexity within the denervated zone, but dendritic spines still formed in the absence of glutamatergic nerve terminals. Electron micrographs confirmed the lack of intact presynaptic terminals apposing spines on mature cells and on newborn neurons. Newborn neurons, but not mature granule cells, had a higher density of dendritic spines in the inner molecular layer postlesion accompanied by an increase in miniature EPSC amplitudes and rise times. Our results indicate that injury causes an increase in newborn neurons and lamina-specific synaptic reorganization indicative of enhanced plasticity. The presence of de novo dendritic spines in the denervated zone suggests that the postlesion environment provides the necessary signals for spine formation.
authors.affiliation: Vollum Institute, Oregon Health and Science University (OHSU), Portland, Oregon 97239, USA. perederi@ohsu.edu
authors.forename: Julia V
authors.initials: JV
authors.lastname: Perederiy
authors.forename: Bryan W
authors.initials: BW
authors.lastname: Luikart
authors.forename: Eric K
authors.initials: EK
authors.lastname: Washburn
authors.forename: Eric
authors.initials: E
authors.lastname: Schnell
authors.forename: Gary L
authors.initials: GL
authors.lastname: Westbrook
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000473:pathology* / Q000503:physiopathology* / Q000517:prevention & control; D001973:Bromodeoxyuridine / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure; D018891:Dentate Gyrus / Q000166:cytology*; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005822:Genetic Vectors / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D016014:Linear Models; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques / Q000379:methods; D019580:Perforant Pathway / Q000293:injuries; D011333:Pro-Opiomelanocortin / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016622:Silver Staining; D018709:Statistics, Nonparametric; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016760:Proto-Oncogene Proteins c-fos; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D011333:Pro-Opiomelanocortin; D016291:Dizocilpine Maleate; D001973:Bromodeoxyuridine