BACKGROUND AND AIMS: Homeostatic plasticity is a regulatory mechanism which allows neurons to maintain a stable level of activity despite of the sustained alterations in neuronal network. Regulation of this form of plasticity is based on global changes of synaptic strength achieved by the alteration in AMPA (α-amino3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor levels on postsynaptic membrane. The process is called synaptic scaling and can be controlled on a transcriptional level. Arc (Activity-regulated cytoskeleton-association protein) accelerates endocytosis of AMPA-type glutamate receptors (AMPARs) and reduces their surface exposure during overexcitation. Our aim was to investigate if the transcription factor SRF (Serum Response Factor) may regulate homeostatic plasticity. METHODS: To increase neuronal activity in vitro we applied widely used model of homeostatic plasticity where hippocampal neurons were treated with 20 μM gabazine (GABAA antagonist) for 24 or 48 hours. RESULTS: Study revealed long-lasting stimulation with gabazine leads to the induction of SRF-driven transcription. We also detected upregulation of Arc protein 24 h after stimulation in control cells had abolished in neurons, in which the level of SRF has been decreased by a specific shRNA. Study revealed that SRF depleted neurons had lower level of surface GluR1 subunits comparing to control cells in basal condition. However, upon prolonged stimulation, loss of SRF results in increased incorporation of GluR1 to the synapses surface in contrast to control cells where decreased level of AMPARs was observed. Analysis of miniature excitatory postsynaptic currents (mEPSCs) confirmed decrease of AMPARs amplitude in control cells in response to stimulation. Conversely, loss of SRF led to increased AMPARs amplitude and abolished homeostatic scaling down of AMPARs. CONCLUSION: Our preliminary data suggests lack of SRF inhibits neurons ability to decrease synaptic strength in response to overexcitation in hippocampal neurons in vitro.
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