Neuronal Rac1 is required for learning-evoked neurogenesis

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

SN - 0270-6474

VL - 33

SP - 12229

EP - 12241

JO - Journal of Neuroscience

JF - Journal of Neuroscience

IS - 30

ER -