Loss of leptin receptors on hypothalamic POMC neurons alters synaptic inhibition

Sung Kun Chun, Young-Hwan Jo

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Adaptive changes in hypothalamic neural circuitry occur in response to alterations in nutritional status. This plasticity at hypothalamic synapses contributes to the control of food intake and body weight. Here we show that genetic ablation of leptin receptor gene expression in proopiomelanocortin (POMC) neurons (POMC: Lepr-/- GFP) induces alterations at synapses on POMC neurons in the arcuate nucleus of the hypothalamus. Our studies reveal that POMC: Lepr-/- GFP mice have decreased frequency of spontaneous GABAergic, but not glutamatergic, postsynaptic currents at synapses on POMC neurons. The decay time course of GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) onto POMC neurons in POMC: Lepr-/- GFP mice is significantly slower than that of sIPSCs in control animals. While analysis of individual miniature IPSCs shows lowered baseline activity, this tonic decrease is associated with an increased amplitude and slow decay of mini-IPSCs onto POMC neurons in POMC: Lepr-/- GFP mice. Moreover, POMC neurons receive greater total ionic flux per GABAergic event in the absence of leptin receptor signaling. In addition, treatment with the alpha 3 subunit-containing GABA A receptor modulator SB-205384 enhances GABAergic transmission only onto POMC neurons in POMC: Lepr-/- GFP mice. Single-cell RT-PCR analysis further supports the expression of the alpha 3 subunit of the GABA A receptor on POMC neurons in POMC: Lepr-/- GFP mice. Finally, the responses to the GABAA receptor agonist isoguvacine of POMC neurons are significantly smaller in POMC: Lepr-/- GFP than in control animals. Therefore our present work demonstrates that loss of leptin signaling in POMC neurons induces synaptic alterations at POMC synapses that may play an essential role in energy homeostasis.

Original languageEnglish (US)
Pages (from-to)2321-2328
Number of pages8
JournalJournal of Neurophysiology
Volume104
Issue number5
DOIs
StatePublished - Nov 2010

Fingerprint

Leptin Receptors
Pro-Opiomelanocortin
Neurons
Synapses
Inhibitory Postsynaptic Potentials
GABA-A Receptors
GABA-A Receptor Agonists
Synaptic Potentials
Arcuate Nucleus of Hypothalamus

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Loss of leptin receptors on hypothalamic POMC neurons alters synaptic inhibition. / Chun, Sung Kun; Jo, Young-Hwan.

In: Journal of Neurophysiology, Vol. 104, No. 5, 11.2010, p. 2321-2328.

Research output: Contribution to journalArticle

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