Neuronal Rac1 is required for learning-evoked neurogenesis
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Neuronal Rac1 is required for learning-evoked neurogenesis. / Haditsch, Ursula; Anderson, Matthew P; Freewoman, Julia; Cord, Branden; Babu, Harish; Brakebusch, Cord Herbert; Palmer, Theo D.
In: Journal of Neuroscience, Vol. 33, No. 30, 24.07.2013, p. 12229-41.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Neuronal Rac1 is required for learning-evoked neurogenesis
AU - Haditsch, Ursula
AU - Anderson, Matthew P
AU - Freewoman, Julia
AU - Cord, Branden
AU - Babu, Harish
AU - Brakebusch, Cord Herbert
AU - Palmer, Theo D
PY - 2013/7/24
Y1 - 2013/7/24
N2 - 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.
AB - 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.
KW - Adult Stem Cells
KW - Animals
KW - Antigens, Differentiation
KW - Brain-Derived Neurotrophic Factor
KW - Cell Proliferation
KW - Cell Survival
KW - Green Fluorescent Proteins
KW - Hippocampus
KW - Male
KW - Maze Learning
KW - Memory, Long-Term
KW - Mice
KW - Mice, Knockout
KW - Mitosis
KW - Neural Stem Cells
KW - Neurogenesis
KW - Neuronal Plasticity
KW - Neurons
KW - Neuropeptides
KW - Receptor, trkB
KW - Receptors, AMPA
KW - Space Perception
KW - rac GTP-Binding Proteins
KW - rac1 GTP-Binding Protein
U2 - 10.1523/JNEUROSCI.2939-12.2013
DO - 10.1523/JNEUROSCI.2939-12.2013
M3 - Journal article
C2 - 23884931
VL - 33
SP - 12229
EP - 12241
JO - The Journal of neuroscience : the official journal of the Society for Neuroscience
JF - The Journal of neuroscience : the official journal of the Society for Neuroscience
SN - 0270-6474
IS - 30
ER -
ID: 108162803