Nature Neuroscience8, 759 - 767 (2005)
Published online: 8 May 2005; | doi:10.1038/nn1462
SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability
Narendrakumar Ramanan1, 2, Ying Shen1, Sarah Sarsfield1, 2, Thomas Lemberger3, Günther Schütz3, David J Linden1
& David D Ginty1, 2
1
Department of Neuroscience, 725 North Wolfe Street, Preclinical Teaching Building Room 1015, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
2
Howard Hughes Medical Institute, 725 North Wolfe Street, Preclinical Teaching Building Room 1015, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
3
Molecular Biology of the Cell I, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Correspondence should be addressed to David D Ginty dginty@jhmi.edu
Synaptic activity-dependent gene expression is critical for certain forms of neuronal plasticity and survival in the mammalian nervous system, yet the mechanisms by which coordinated regulation of activity-induced genes supports neuronal function is unclear. Here, we show that deletion of serum response factor (SRF) in specific neuronal populations in adult mice results in profound deficits in activity-dependent immediate early gene expression, but components of upstream signaling pathways and cyclic AMP−response element binding protein (CREB)-dependent transactivation remain intact. Moreover, SRF-deficient CA1 pyramidal neurons show attenuation of long-term synaptic potentiation, a model for neuronal information storage. Furthermore, in contrast to the massive neurodegeneration seen in adult mice lacking CREB family members, SRF-deficient adult neurons show normal morphologies and basal excitatory synaptic transmission. These findings indicate that the transcriptional events underlying neuronal survival and plasticity are dissociable and that SRF plays a prominent role in use-dependent modification of synaptic strength in the adult brain.
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