Projects per year
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.
Original language | English |
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Article number | e25755 |
Number of pages | 25 |
Journal | eLife |
Volume | 6 |
DOIs | |
Publication status | Published - 1 Aug 2017 |
Keywords
- AMPA receptors
- calcium permeability
- mouse
- neuroscience
- plasticity
- POMC neurons
Projects
- 2 Finished
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NHMRC Research Fellowship
National Health and Medical Research Council (NHMRC) (Australia)
1/01/15 → 31/12/19
Project: Research
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Effects of melanocortin neurons on systemic glucose homeostasis
Cowley, M. & Enriori, P.
National Health and Medical Research Council (NHMRC) (Australia)
1/01/14 → 31/12/17
Project: Research