title: Neuronal Rac1 is required for learning-evoked neurogenesis.
abstract: Hippocampus-dependent learning and memory relies on synaptic plasticity as well as network adaptations provided by the addition of adult-born neurons. We have previously shown that activity-induced intracellular signaling through the Rho family small GTPase Rac1 is necessary in forebrain projection neurons for normal synaptic plasticity in vivo, and here we show that selective loss of neuronal Rac1 also impairs the learning-evoked increase in neurogenesis in the adult mouse hippocampus. Earlier work has indicated that experience elevates the abundance of adult-born neurons in the hippocampus primarily by enhancing the survival of neurons produced just before the learning event. Loss of Rac1 in mature projection neurons did reduce learning-evoked neurogenesis but, contrary to our expectations, these effects were not mediated by altering the survival of young neurons in the hippocampus. Instead, loss of neuronal Rac1 activation selectively impaired a learning-evoked increase in the proliferation and accumulation of neural precursors generated during the learning event itself. This indicates that experience-induced alterations in neurogenesis can be mechanistically resolved into two effects: (1) the well documented but Rac1-independent signaling cascade that enhances the survival of young postmitotic neurons; and (2) a previously unrecognized Rac1-dependent signaling cascade that stimulates the proliferative production and retention of new neurons generated during learning itself.
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA. ursula.haditsch@stanford.edu
authors.forename: Ursula
authors.initials: U
authors.lastname: Haditsch
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Anderson
authors.forename: Julia
authors.initials: J
authors.lastname: Freewoman
authors.forename: Branden
authors.initials: B
authors.lastname: Cord
authors.forename: Harish
authors.initials: H
authors.lastname: Babu
authors.forename: Cord
authors.initials: C
authors.lastname: Brakebusch
authors.forename: Theo D
authors.initials: TD
authors.lastname: Palmer
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000502:physiology*; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D057567:Memory, Long-Term / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis / Q000502:physiology; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D055495:Neurogenesis / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D018091:Receptors, AMPA / Q000502:physiology; D013028:Space Perception / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020830:rac1 GTP-Binding Protein; D000097642:GADD45 Proteins
chemical_list: D000943:Antigens, Differentiation; D019208:Brain-Derived Neurotrophic Factor; D049452:Green Fluorescent Proteins; D009479:Neuropeptides; D020813:Receptor, trkB; D018091:Receptors, AMPA; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; C490125:Gadd45b protein, mouse; D000097642:GADD45 Proteins; C484602:Rac1 protein, mouse