title: BDNF-induced LTP is associated with rapid Arc/Arg3.1-dependent enhancement in adult hippocampal neurogenesis.
abstract: Adult neurogenesis in the hippocampus is a remarkable phenomenon involved in various aspects of learning and memory as well as disease pathophysiology. Brain-derived neurotrophic factor (BDNF) represents a major player in the regulation of this unique form of neuroplasticity, yet the mechanisms underlying its pro-neurogenic actions remain unclear. Here, we examined the effects associated with brief (25 min), unilateral infusion of BDNF in the rat dentate gyrus. Acute BDNF infusion induced long-term potentiation (LTP) of medial perforant path-evoked synaptic transmission and, concomitantly, enhanced hippocampal neurogenesis bilaterally, reflected by increased dentate gyrus BrdU + cell numbers. Importantly, inhibition of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) translation through local, unilateral infusion of anti-sense oligodeoxynucleotides (ArcAS) prior to BDNF infusion blocked both BDNF-LTP induction and the associated pro-neurogenic effects. Notably, basal rates of proliferation and newborn cell survival were unaltered in homozygous Arc/Arg3.1 knockout mice. Taken together these findings link the pro-neurogenic effects of acute BDNF infusion to induction of Arc/Arg3.1-dependent LTP in the adult rodent dentate gyrus.
authors.affiliation: Department of Biomedicine and KG Jebsen Centre for Research on Neuropsychiatric Disorders, Jonas Lies vei 91, University of Bergen, 5009 Bergen, Norway.
authors.forename: Sjoukje D
authors.initials: SD
authors.lastname: Kuipers
authors.affiliation: Department of Biomedicine and KG Jebsen Centre for Research on Neuropsychiatric Disorders, Jonas Lies vei 91, University of Bergen, 5009 Bergen, Norway.
authors.forename: Andrea
authors.initials: A
authors.lastname: Trentani
authors.affiliation: Department of Biomedicine and KG Jebsen Centre for Research on Neuropsychiatric Disorders, Jonas Lies vei 91, University of Bergen, 5009 Bergen, Norway.
authors.forename: Adrian
authors.initials: A
authors.lastname: Tiron
authors.affiliation: Institute for Molecular and Cellular Cognition, Center for Molecular Neurobiology (ZMNH) University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Mao
authors.affiliation: Institute for Molecular and Cellular Cognition, Center for Molecular Neurobiology (ZMNH) University Medical Center Hamburg-Eppendorf, Falkenried 94, 20251 Hamburg, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kuhl
authors.affiliation: Department of Biomedicine and KG Jebsen Centre for Research on Neuropsychiatric Disorders, Jonas Lies vei 91, University of Bergen, 5009 Bergen, Norway.
authors.forename: Clive R
authors.initials: CR
authors.lastname: Bramham
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism*; D005071:Evoked Potentials / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D055495:Neurogenesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein