SRF mediates activity-induced gene expression and synaptic plasticity but not neuronal viability

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Synaptic activity-dependent gene expression is vital for neuronal plasticity and survival.
• Mechanisms linking gene regulation to neuronal function remain incompletely understood.

Purpose of the Study:

• To investigate the role of serum response factor (SRF) in activity-dependent gene expression and neuronal function in adult mice.
• To determine if SRF is essential for neuronal survival or synaptic plasticity.

Main Methods:

• Deletion of SRF in specific neuronal populations in adult mice.
• Analysis of immediate early gene expression.
• Assessment of cyclic AMP-response element binding protein (CREB)-dependent transactivation.
• Electrophysiological recordings of long-term potentiation (LTP) in CA1 pyramidal neurons.
• Evaluation of neuronal morphology and basal synaptic transmission.

Main Results:

• SRF deletion caused significant deficits in activity-dependent immediate early gene expression.
• Upstream signaling pathways and CREB-dependent transactivation remained functional in SRF-deficient neurons.
• SRF-deficient CA1 neurons exhibited attenuated long-term potentiation.
• SRF deficiency did not lead to neurodegeneration or affect basal synaptic transmission, unlike CREB-deficient mice.

Conclusions:

• Neuronal survival and plasticity mechanisms are dissociable.
• SRF plays a critical role in use-dependent synaptic strength modification in the adult brain.
• SRF is essential for specific forms of synaptic plasticity, distinct from its role in neuronal survival.