SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability.
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.
Ramanan
Narendrakumar
N
Department of Neuroscience, 725 North Wolfe Street, Preclinical Teaching Building Room 1015, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Shen
Ying
Y
Sarsfield
Sarah
S
Lemberger
Thomas
T
Schütz
Günther
G
Linden
David J
DJ
Ginty
David D
DD
D000818:Animals; D002470:Cell Survival / Q000502:physiology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D017781:Genes, Immediate-Early / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009473:Neuronal Plasticity / Q000235:genetics*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics*; D015533:Transcriptional Activation / Q000502:physiology
D017362:Cyclic AMP Response Element-Binding Protein; D026362:Serum Response Factor