Haditsch, Ursula3; Anderson, Matthew P4; Freewoman, Julia4; Cord, Branden4; Babu, Harish4; Brakebusch, Cord Herbert6; Palmer, Theo D4
1 Section of Molecular Pathology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet2 Department of Biomedical Sciences, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet3 Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California 94305, USA. firstname.lastname@example.org unknown5 Brakebusch Group, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet6 Brakebusch Group, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet
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.
Journal of Neuroscience, 2013, Vol 33, Issue 30, p. 12229-41