Plasticity of calcium-permeable AMPA glutamate receptors in Pro-opiomelanocortin neurons
Shigetomo Suyama,
Alexandra Ralevski,
Zhong-Wu Liu,
Marcelo O Dietrich,
Toshihiko Yada,
Stephanie E Simonds,
Michael A Cowley,
Xiao-Bing Gao,
Sabrina Diano,
Tamas L Horvath
Affiliations
Shigetomo Suyama
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, United States; Division of Integrative Physiology, Department of Physiology, Jichi Medical University, Tochigi, Japan
Alexandra Ralevski
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, United States
Zhong-Wu Liu
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, United States
Marcelo O Dietrich
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, United States
Toshihiko Yada
Division of Integrative Physiology, Department of Physiology, Jichi Medical University, Tochigi, Japan
Stephanie E Simonds
Biomedicine Discovery Institute, Department of Physiology, Monash University, Clayton, Australia
Michael A Cowley
Biomedicine Discovery Institute, Department of Physiology, Monash University, Clayton, Australia
Xiao-Bing Gao
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, United States
Sabrina Diano
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, United States; Departments of Ob/Gyn and Reproductive Sciences, Yale University School of Medicine, New Haven, United States; Department of Neurobiology, Yale University School of Medicine, New Haven, United States
Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, United States; Departments of Ob/Gyn and Reproductive Sciences, Yale University School of Medicine, New Haven, United States; Department of Neurobiology, Yale University School of Medicine, New Haven, United States; Department of Anatomy and Histology, University of Veterinary Medicine, Budapest, Hungary
POMC neurons integrate metabolic signals from the periphery. Here, we show in mice that food deprivation induces a linear current-voltage relationship of AMPAR-mediated excitatory postsynaptic currents (EPSCs) in POMC neurons. Inhibition of EPSCs by IEM-1460, an antagonist of calcium-permeable (Cp) AMPARs, diminished EPSC amplitude in the fed but not in the fasted state, suggesting entry of GluR2 subunits into the AMPA receptor complex during food deprivation. Accordingly, removal of extracellular calcium from ACSF decreased the amplitude of mEPSCs in the fed but not the fasted state. Ten days of high-fat diet exposure, which was accompanied by elevated leptin levels and increased POMC neuronal activity, resulted in increased expression of Cp-AMPARs on POMC neurons. Altogether, our results show that entry of calcium via Cp-AMPARs is inherent to activation of POMC neurons, which may underlie a vulnerability of these neurons to calcium overload while activated in a sustained manner during over-nutrition.
