First, the authors tested the effects of noradrenaline on GluR1 phosphorylation in hippocampal slices. They found that it induced phosphorylation at two sites, Ser845 and Ser831, and that this was dependent on β-adrenergic receptor (β-AR) signalling. Similar results were obtained in hippocampi from mice that had been exposed to adrenaline or fox urine (which is known to induce innate fear).
Increasing the number of AMPA receptors in the postsynaptic membrane is a mechanism that is thought to underlie the expression of long-term potentiation. Therefore, the authors looked at GluR1 trafficking to synapses to determine whether phosphorylation of GluR1 by noradrenaline facilitates this process. Using GluR1 tagged with green fluorescent protein, in combination with electrophysiological methods, they showed that, under a low-frequency electrical stimulus (which is insufficient by itself to facilitate the synaptic delivery of GluR1), noradrenaline induces the synaptic incorporation of GluR1. In neurons transfected with a GluR1DD construct, in which amino-acid mutations mimic the permanent phosphorylation of Ser845 and Ser831, a low-frequency electrical stimulus alone induced synaptic delivery of GluR1. To confirm the role of phosphorylation at these sites, the authors used cells expressing GluR1AA, in which phosphorylation at Ser845 and Ser831 is prevented, and found that the application of noradrenaline under a low-frequency electrical stimulus did not result in the synaptic incorporation of GluR1. These results suggest that phosphorylation at Ser845 and Ser831 is both sufficient and necessary for the synaptic delivery of the GluR1-containing AMPA receptors.
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