Abstract
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.
Highlights
Proopiomelanocortin (POMC)-producing neurons in the arcuate nucleus (ARC) of the hypothalamus are well known to control satiety and glucose metabolism (Horvath, 2006)
To test the hypothesis that leptin may be involved in the regulation of the AMPA receptor complex, we examined the effects of leptin on the rectification of AMPAR-excitatory postsynaptic currents (EPSCs) in POMC neurons in the ARC of fasted mice
We demonstrated that excitatory inputs onto POMC neurons in the ARC facilitate synaptic changes that are dependent on the metabolic state
Summary
Proopiomelanocortin (POMC)-producing neurons in the arcuate nucleus (ARC) of the hypothalamus are well known to control satiety and glucose metabolism (Horvath, 2006). POMC neurons integrate peripheral metabolic signals such as leptin, insulin and glucose, and alter other circuits to adjust behavior and autonomic regulation, in part, through melanocortin receptor signaling (Cone, 2005; Gao and Horvath, 2007; Horvath, 2006; Koch et al, 2015; Mountjoy et al, 1992; Ollmann et al, 1997). In addition to peripheral metabolic signals, synaptic transmission is required to regulate POMC neuronal activity and body weight (Branco et al, 2016).
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