GABA Release from Proopiomelanocortin Neurons

Shane T. Hentges, Mitsuru Nishiyama, Linda S. Overstreet, Mary Stenzel-Poore, John T. Williams, Malcolm J. Low

Research output: Contribution to journalArticlepeer-review

124 Scopus citations


Neural networks controlling food intake and energy homeostasis clearly involve proopiomelanocortin (POMC) neurons and their peptide transmitters, α-melanocyte-stimulating hormone from arcuate POMC neurons potently reduces food intake, whereas arcuate neuropeptide Y (NPY) neurons act in opposition to stimulate food intake. In addition to orexigenic peptides, NPY neurons also release the inhibitory neurotransmitter GABA, which can act in a local circuit to inhibit POMC neuron activity. Whether or not reciprocal inhibition could occur has not yet been determined, because the presence of a rapid neurotransmitter in POMC neurons has not been demonstrated previously. Here, we used primary cultures of fluorescently labeled POMC neurons that had formed recurrent synapses (autapses) to detect the release of neurotransmitter. When an action potential was evoked in the axon of a POMC neuron with autapses, a short-latency synaptic current was recorded in the same cell. The autaptic current was abolished by GABAA receptor antagonists and substantially inhibited by opioids. Double-label in situ RNA hybridization for POMC and glutamic acid decarboxylase, the GABA synthetic enzyme, revealed colocalization of mRNAs in approximately one-third of POMC neurons in vivo. Our results suggest that these neurons can exert rapid inhibitory effects via the release of GABA, in addition to the more sustained actions provided by POMC peptides. However, this rapid inhibition may not play a major role within local hypothalamic circuits, but rather is likely to be important in more distant projection areas as indicated by the colocalization of vesicular GABA transporter immunoreactivity predominately in extrahypothalamic POMC terminals.

Original languageEnglish (US)
Pages (from-to)1578-1583
Number of pages6
JournalJournal of Neuroscience
Issue number7
StatePublished - Feb 18 2004


  • Arcuate nucleus
  • Autapse
  • Green fluorescent protein
  • Hypothalamus
  • Neuron culture
  • Opioids
  • Transgenic mouse

ASJC Scopus subject areas

  • General Neuroscience


Dive into the research topics of 'GABA Release from Proopiomelanocortin Neurons'. Together they form a unique fingerprint.

Cite this