Presynaptic melanocortin-4 receptors on vagal afferent fibers modulate the excitability of rat nucleus tractus solitarius neurons

Shuxia Wan, Kirsteen N. Browning, F. Holly Coleman, Gregory Sutton, Hiyuan Zheng, Andrew Butler, Hans Rudolf Berthoud, R. Alberto Travagli

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

The nucleus tractus solitarius (NTS) integrates visceral sensory signals with information from the forebrain to control homeostatic functions, including food intake. Melanocortin 3/4 receptor (MC3/4R) ligands administered directly to the caudal brainstem powerfully modulate meal size but not frequency, suggesting the enhancement of visceral satiety signals. Using whole-cell recordings from rat brainstem slices, we examined the effects of melanocortin ligands, α-melanocyte-stimulating hormone (αMSH) and melanotan II (MTII), on EPSC in NTS neurons. Thirty-two percent of NTS neurons responded to perfusion with MTII or αMSH with either an increase (24%) or a decrease (8%) in the frequency, but not amplitude, of spontaneous EPSCs; the effects of MTII were abolished by pretreatment with SHU9119. After surgical vagal deafferentation, only four of 34 (9%) NTS neurons responded to MTII with an increase in EPSC frequency. When EPSCs were evoked by electrical stimulation of the tractus solitarius in Krebs' solution with 2.4mM Ca 2+ e , αMSH and MTII increased the amplitude in six of the 28 neurons tested, decreased amplitude in 14 with no effect in the remaining eight neurons. In four of six neurons unresponsive to MTII, decreasing Ca 2+ e levels to 1.5mM uncovered an excitatory effect of MTII on EPSC amplitude. Reverse transcription-PCR analysis revealed the presence of MC4R, but not MC3R, in nodose ganglia. These results show that MC4R signaling leads mainly to presynaptic modulation of glutamatergic synaptic transmission and suggest that melanocortinergic-induced decrease of food intake may occur via enhancement of vagal afferent satiation signals from the gastrointestinal tract.

Original languageEnglish (US)
Pages (from-to)4957-4966
Number of pages10
JournalJournal of Neuroscience
Volume28
Issue number19
DOIs
StatePublished - May 7 2008

Fingerprint

Receptor, Melanocortin, Type 4
Solitary Nucleus
Neurons
Melanocyte-Stimulating Hormones
Brain Stem
Receptor, Melanocortin, Type 3
Eating
Nodose Ganglion
Melanocortins
Satiation
Ligands
Patch-Clamp Techniques
Prosencephalon
melanotan-II
Synaptic Transmission
Electric Stimulation
Reverse Transcription
Meals
Gastrointestinal Tract
Perfusion

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Wan, Shuxia ; Browning, Kirsteen N. ; Coleman, F. Holly ; Sutton, Gregory ; Zheng, Hiyuan ; Butler, Andrew ; Berthoud, Hans Rudolf ; Travagli, R. Alberto. / Presynaptic melanocortin-4 receptors on vagal afferent fibers modulate the excitability of rat nucleus tractus solitarius neurons. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 19. pp. 4957-4966.
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abstract = "The nucleus tractus solitarius (NTS) integrates visceral sensory signals with information from the forebrain to control homeostatic functions, including food intake. Melanocortin 3/4 receptor (MC3/4R) ligands administered directly to the caudal brainstem powerfully modulate meal size but not frequency, suggesting the enhancement of visceral satiety signals. Using whole-cell recordings from rat brainstem slices, we examined the effects of melanocortin ligands, α-melanocyte-stimulating hormone (αMSH) and melanotan II (MTII), on EPSC in NTS neurons. Thirty-two percent of NTS neurons responded to perfusion with MTII or αMSH with either an increase (24{\%}) or a decrease (8{\%}) in the frequency, but not amplitude, of spontaneous EPSCs; the effects of MTII were abolished by pretreatment with SHU9119. After surgical vagal deafferentation, only four of 34 (9{\%}) NTS neurons responded to MTII with an increase in EPSC frequency. When EPSCs were evoked by electrical stimulation of the tractus solitarius in Krebs' solution with 2.4mM Ca 2+ e , αMSH and MTII increased the amplitude in six of the 28 neurons tested, decreased amplitude in 14 with no effect in the remaining eight neurons. In four of six neurons unresponsive to MTII, decreasing Ca 2+ e levels to 1.5mM uncovered an excitatory effect of MTII on EPSC amplitude. Reverse transcription-PCR analysis revealed the presence of MC4R, but not MC3R, in nodose ganglia. These results show that MC4R signaling leads mainly to presynaptic modulation of glutamatergic synaptic transmission and suggest that melanocortinergic-induced decrease of food intake may occur via enhancement of vagal afferent satiation signals from the gastrointestinal tract.",
author = "Shuxia Wan and Browning, {Kirsteen N.} and Coleman, {F. Holly} and Gregory Sutton and Hiyuan Zheng and Andrew Butler and Berthoud, {Hans Rudolf} and Travagli, {R. Alberto}",
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Presynaptic melanocortin-4 receptors on vagal afferent fibers modulate the excitability of rat nucleus tractus solitarius neurons. / Wan, Shuxia; Browning, Kirsteen N.; Coleman, F. Holly; Sutton, Gregory; Zheng, Hiyuan; Butler, Andrew; Berthoud, Hans Rudolf; Travagli, R. Alberto.

In: Journal of Neuroscience, Vol. 28, No. 19, 07.05.2008, p. 4957-4966.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Presynaptic melanocortin-4 receptors on vagal afferent fibers modulate the excitability of rat nucleus tractus solitarius neurons

AU - Wan, Shuxia

AU - Browning, Kirsteen N.

AU - Coleman, F. Holly

AU - Sutton, Gregory

AU - Zheng, Hiyuan

AU - Butler, Andrew

AU - Berthoud, Hans Rudolf

AU - Travagli, R. Alberto

PY - 2008/5/7

Y1 - 2008/5/7

N2 - The nucleus tractus solitarius (NTS) integrates visceral sensory signals with information from the forebrain to control homeostatic functions, including food intake. Melanocortin 3/4 receptor (MC3/4R) ligands administered directly to the caudal brainstem powerfully modulate meal size but not frequency, suggesting the enhancement of visceral satiety signals. Using whole-cell recordings from rat brainstem slices, we examined the effects of melanocortin ligands, α-melanocyte-stimulating hormone (αMSH) and melanotan II (MTII), on EPSC in NTS neurons. Thirty-two percent of NTS neurons responded to perfusion with MTII or αMSH with either an increase (24%) or a decrease (8%) in the frequency, but not amplitude, of spontaneous EPSCs; the effects of MTII were abolished by pretreatment with SHU9119. After surgical vagal deafferentation, only four of 34 (9%) NTS neurons responded to MTII with an increase in EPSC frequency. When EPSCs were evoked by electrical stimulation of the tractus solitarius in Krebs' solution with 2.4mM Ca 2+ e , αMSH and MTII increased the amplitude in six of the 28 neurons tested, decreased amplitude in 14 with no effect in the remaining eight neurons. In four of six neurons unresponsive to MTII, decreasing Ca 2+ e levels to 1.5mM uncovered an excitatory effect of MTII on EPSC amplitude. Reverse transcription-PCR analysis revealed the presence of MC4R, but not MC3R, in nodose ganglia. These results show that MC4R signaling leads mainly to presynaptic modulation of glutamatergic synaptic transmission and suggest that melanocortinergic-induced decrease of food intake may occur via enhancement of vagal afferent satiation signals from the gastrointestinal tract.

AB - The nucleus tractus solitarius (NTS) integrates visceral sensory signals with information from the forebrain to control homeostatic functions, including food intake. Melanocortin 3/4 receptor (MC3/4R) ligands administered directly to the caudal brainstem powerfully modulate meal size but not frequency, suggesting the enhancement of visceral satiety signals. Using whole-cell recordings from rat brainstem slices, we examined the effects of melanocortin ligands, α-melanocyte-stimulating hormone (αMSH) and melanotan II (MTII), on EPSC in NTS neurons. Thirty-two percent of NTS neurons responded to perfusion with MTII or αMSH with either an increase (24%) or a decrease (8%) in the frequency, but not amplitude, of spontaneous EPSCs; the effects of MTII were abolished by pretreatment with SHU9119. After surgical vagal deafferentation, only four of 34 (9%) NTS neurons responded to MTII with an increase in EPSC frequency. When EPSCs were evoked by electrical stimulation of the tractus solitarius in Krebs' solution with 2.4mM Ca 2+ e , αMSH and MTII increased the amplitude in six of the 28 neurons tested, decreased amplitude in 14 with no effect in the remaining eight neurons. In four of six neurons unresponsive to MTII, decreasing Ca 2+ e levels to 1.5mM uncovered an excitatory effect of MTII on EPSC amplitude. Reverse transcription-PCR analysis revealed the presence of MC4R, but not MC3R, in nodose ganglia. These results show that MC4R signaling leads mainly to presynaptic modulation of glutamatergic synaptic transmission and suggest that melanocortinergic-induced decrease of food intake may occur via enhancement of vagal afferent satiation signals from the gastrointestinal tract.

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