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Amylin excites a subset of proopiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) via enhancing the excitatory glutamatergic synaptic inputs
Author(s) -
Gu Yan,
Fan Wei
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1166.6
Subject(s) - amylin , excitatory postsynaptic potential , glutamatergic , arc (geometry) , chemistry , postsynaptic current , medicine , neuroscience , endocrinology , arcuate nucleus , slice preparation , glutamate receptor , biology , inhibitory postsynaptic potential , nucleus , electrophysiology , biochemistry , insulin , receptor , geometry , mathematics , islet
Amylin, released from pancreas in response to nutrient ingestion, exerts anorexic effects. The ARC POMC neurons are essential for energy homeostasis by integrating a variety of peripheral and central signals that regulate energy balance. Amylin binding sites exist in the ARC. We examined the action of amylin on the ARC POMC neurons in hypothalamic slices of POMC‐EGFP transgenic mice. Bath application of amylin (1‐1000 nM) dose‐dependently increased the firing rate in 36 out of 55 POMC cells tested under loose‐patch extracellular recording. In the presence of kynurenic acid and picrotoxin to block synaptic transmission, amylin did not significantly change the firing rate of ARC POMC neurons, suggestive of an underlying presynaptic mechanism. Under voltage clamp recording, bath application of amylin (200 nM) increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in 7 out of 17 POMC cells, and increased the amplitude of sEPSCs in 12 out of 17 POMC cells, while increased the frequency of miniature EPSCs (mEPSCs) but decreased the amplitude of mEPSCs in 6 out of 11 POMC cells tested, respectively. These data suggest that amylin excites a subset of ARC POMC neurons via enhancing the excitatory glutamatergic synaptic inputs. (We thank Dr. Malcolm J Low for providing POMC transgenic mice and Jonathan G Murphy for help with genotyping animals, Supported by NIH grant DK62179 and CSWR foundation.)