Proopiomelanocortin expression in both GABA and glutamate neurons.
Proopiomelanocortin (POMC) neurons have been intensively studied because of their essential role in regulating energy balance and body weight. Many effects of POMC neurons can be attributed to their release of cognate neuropeptides from secretory granules in axon terminals. However, these neurons also synaptically release non-peptide neurotransmitters. The aim of this study was to settle the controversy whether there are separate populations of POMC neurons that release GABA or glutamate. Transgenic mice expressing a red fluorescent protein [Discosoma red (DsRed)] driven by Pomc neuronal regulatory elements (POMC-DsRed) were crossed to mice that expressed green fluorescent protein (gfp) in GABAergic neurons (GAD67-gfp). Approximately 40% of POMC neurons in the arcuate nucleus of the double-transgenic mice expressed the GAD67-gfp transgene. In vitro neurotransmitter release was detected using whole-cell electrophysiologic recordings in cultured GAD67-gfp-positive and GAD67-gfp-negative POMC neurons that had formed recurrent synapses (autapses). Autapses from GAD67-gfp-positive neurons were uniformly GABAergic. In contrast, autapses from the GAD67-gfp-negative POMC neurons exclusively exhibited postsynaptic currents mediated by glutamate. Together, these results indicate that there are two subpopulations of POMC neurons in the arcuate nucleus differentiated by their amino acid neurotransmitter phenotype. Whole-cell voltage-clamp recordings from POMC neurons in live brain slices indicated that GABAergic and glutamatergic POMC neurons are under similar presynaptic and postsynaptic regulation, although the GABAergic POMC neurons are smaller and have higher input resistance. GABAergic and glutamatergic POMC neurons may mediate distinct aspects of POMC neuron function, including the regulation of energy homeostasis.
Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523-1617, USA. hentgess@colostate.edu
Shane T
ST
Hentges
Veronica
V
Otero-Corchon
Reagan L
RL
Pennock
Connie M
CM
King
Malcolm J
MJ
Low
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000097573:Red Fluorescent Protein
D000324:Adrenocorticotropic Hormone; D005968:Glutamate Decarboxylase; D018698:Glutamic Acid; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D011333:Pro-Opiomelanocortin; D005680:gamma-Aminobutyric Acid; D000097573:Red Fluorescent Protein; C402565:glutamate decarboxylase 1