Adiponectin promotes AMPA receptor trafficking and enhances excitatory synaptic transmission at hippocampal synapses via AMP‐activated protein kinase signalling
Alexandra Soca, Patricia Raposo Afonso, Valentin Morfin, James Cantley, Jenni HarveyBackground and Purpose
Peripherally derived adiponectin crosses the blood–brain barrier and targets severa0l brain regions. Adiponectin receptors are highly expressed in the hippocampus, and play a pro‐cognitive role as adiponectin markedly influences the functioning of hippocampal synapses. Trafficking of AMPA receptors underlies activity‐dependent hippocampal synaptic plasticity, but it is unclear if adiponectin influences this process. Here, we examined the effects of he adiponectin receptor agonist, AdipoRon, on AMPA receptor trafficking and hippocampal excitatory synaptic function.
Experimental Approach
Immunocytochemistry combined with confocal microscopy was used to monitor the surface expression of the AMPA receptor subunit, GluA1, in hippocampal neurons cultured from neonatal (P0–4) rats. Extracellular field potential recordings were used to monitor excitatory synaptic transmission in hippocampal slices from juvenile male (P14–24) Sprague Dawley rats.
Key Results
AdipoRon increased GluA1 surface expression and delivered GluA1‐containing AMPA receptors to synapses. In hippocampal slices, AdipoRon increased excitatory synaptic transmission, maintained during recordings, and AdipoRon enhanced hippocampal long‐term potentiation. Effects of AdipoRon on AMPA receptor trafficking involved AdipoRon receptors, as these effects were mirrored by the adiponectin receptor agonist, ADP355 and blocked by the antagonist, ADP400. AdipoRon‐driven increases in surface GluA1 required GluN2A‐containing NMDA receptor activation. Effects of AdipoRon on GluA1 expression and synaptic plasticity involved AMPK signalling.
Conclusions and Implications
These data show that AdipoRon trafficked GluA1‐containing AMPA receptors to synapses and facilitated hippocampal synaptic plasticity via activation of AMPK. These findings have important implications for the role of adiponectin in regulating hippocampal synaptic function in health and disease.