title: High-frequency stimulation induces gradual immediate early gene expression in maturing adult-generated hippocampal granule cells.
abstract: Increasing evidence shows that adult neurogenesis of hippocampal granule cells is advantageous for learning and memory. We examined at which stage of structural maturation and age new granule cells can be activated by strong synaptic stimulation. High-frequency stimulation of the perforant pathway in urethane-anesthetized rats elicited expression of the immediate early genes c-fos, Arc, zif268 and pCREB133 in almost 100% of mature, calbindin-positive granule cells. In contrast, it failed to induce immediate early gene expression in immature doublecortin-positive granule cells. Furthermore, doublecortin-positive neurons did not react with c-fos or Arc expression to mild theta-burst stimulation or novel environment exposure. Endogenous expression of pCREB133 was increasingly present in young cells with more elaborated dendrites, revealing a close correlation to structural maturation. Labeling with bromodeoxyuridine revealed cell age dependence of stimulation-induced c-fos, Arc and zif268 expression, with only a few cells reacting at 21 days, but with up to 75% of cells activated at 35-77 days of cell age. Our results indicate an increasing synaptic integration of maturing granule cells, starting at 21 days of cell age, but suggest a lack of ability to respond to activation with synaptic potentiation on the transcriptional level as long as immature cells express doublecortin.
authors: Institute of Clinical Neuroanatomy, Goethe-University Frankfurt, NeuroScience Center, D-60590 Frankfurt am Main, Germany.
authors: Tassilo
authors: T
authors: Jungenitz
authors: Institute of Clinical Neuroanatomy, Goethe-University Frankfurt, NeuroScience Center, D-60590 Frankfurt am Main, Germany.
authors: Tijana
authors: T
authors: Radic
authors: Institute of Clinical Neuroanatomy, Goethe-University Frankfurt, NeuroScience Center, D-60590 Frankfurt am Main, Germany.
authors: Peter
authors: P
authors: Jedlicka
authors: Institute of Clinical Neuroanatomy, Goethe-University Frankfurt, NeuroScience Center, D-60590 Frankfurt am Main, Germany.
authors: Stephan W
authors: SW
authors: Schwarzacher
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D055592:Biophysical Phenomena / Q000502:physiology*; D050882:CREB-Binding Protein / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D051766:Early Growth Response Protein 1 / Q000378:metabolism; D005106:Exploratory Behavior; D007839:Functional Laterality; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology* / Q000254:growth & development; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D019580:Perforant Pathway / Q000502:physiology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012794:Sialic Acids / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D008869:Microtubule-Associated Proteins; D009124:Muscle Proteins; D039842:Neural Cell Adhesion Molecule L1; D009479:Neuropeptides; C491788:Nol3 protein, rat; D016760:Proto-Oncogene Proteins c-fos; D012794:Sialic Acids; C103469:polysialyl neural cell adhesion molecule; D050882:CREB-Binding Protein; D010751:Phosphopyruvate Hydratase
keywords: Arc; BrdU; LTP; adult neurogenesis; c-fos; pCREB; rat; zif268