Functional organization of presynaptic metabotropic glutamate receptors in vagal brainstem circuits

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

We demonstrated previously that, by suppressing cAMP levels, metabotropic glutamate receptors (mGluRs) play a crucial role in opioid receptor trafficking on GABAergic nerve terminals within gastric brainstem vagal circuits. Using whole-cell patch-clamp recordings, we aimed to correlate the influence of sensory vagal afferent fibers with the functional organization of mGluRs on the synaptic connections between the nucleus tractus solitarius and dorsal motor nucleus of the vagus. Group II mGluRs were identified on both excitatory and inhibitory synapses; the receptor-selective agonist APDC [(2R,4R)-4- aminopyrrolidine-2,4-dicarboxylate] induced a concentration-dependent decrease in glutamatergic and GABAergic synaptic transmission (EC50,∼20 μM for both). The group II mGluRs were activated tonically on GABAergic, but not glutamatergic synapses, as the receptor-selective antagonist (2S)-α-ethylglutamic acid (EGLU; 200 μM) modulated GABA currents only. After selective vagal deafferentation, EGLU was without effect, suggesting that vagal afferent (sensory) fibers are the source of this tonic input. Conversely, group III mGluRs, although not activated tonically, were present on excitatory, but not inhibitory, synapses; in fact, the receptor-selective agonist L-AP-4 [L-(+)-2-amino-4-phosphonbutyric acid] induced a concentration-dependent decrease in glutamatergic synaptic transmission (EC50, ∼2 μM) but had no effect on GABAergic synaptic transmission. Together with our previous results on receptor trafficking, these data suggest that visceral information plays a fundamental role in shaping the response of homeostatic brainstem circuits that receive inputs from higher integrative neuronal centers.

Original languageEnglish (US)
Pages (from-to)8979-8988
Number of pages10
JournalJournal of Neuroscience
Volume27
Issue number34
DOIs
StatePublished - Aug 22 2007

Fingerprint

Metabotropic Glutamate Receptors
Brain Stem
Synaptic Transmission
Synapses
Solitary Nucleus
Acids
Opioid Receptors
gamma-Aminobutyric Acid
Stomach

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

@article{abb3ec21f480470d85bd19fa0ee58beb,
title = "Functional organization of presynaptic metabotropic glutamate receptors in vagal brainstem circuits",
abstract = "We demonstrated previously that, by suppressing cAMP levels, metabotropic glutamate receptors (mGluRs) play a crucial role in opioid receptor trafficking on GABAergic nerve terminals within gastric brainstem vagal circuits. Using whole-cell patch-clamp recordings, we aimed to correlate the influence of sensory vagal afferent fibers with the functional organization of mGluRs on the synaptic connections between the nucleus tractus solitarius and dorsal motor nucleus of the vagus. Group II mGluRs were identified on both excitatory and inhibitory synapses; the receptor-selective agonist APDC [(2R,4R)-4- aminopyrrolidine-2,4-dicarboxylate] induced a concentration-dependent decrease in glutamatergic and GABAergic synaptic transmission (EC50,∼20 μM for both). The group II mGluRs were activated tonically on GABAergic, but not glutamatergic synapses, as the receptor-selective antagonist (2S)-α-ethylglutamic acid (EGLU; 200 μM) modulated GABA currents only. After selective vagal deafferentation, EGLU was without effect, suggesting that vagal afferent (sensory) fibers are the source of this tonic input. Conversely, group III mGluRs, although not activated tonically, were present on excitatory, but not inhibitory, synapses; in fact, the receptor-selective agonist L-AP-4 [L-(+)-2-amino-4-phosphonbutyric acid] induced a concentration-dependent decrease in glutamatergic synaptic transmission (EC50, ∼2 μM) but had no effect on GABAergic synaptic transmission. Together with our previous results on receptor trafficking, these data suggest that visceral information plays a fundamental role in shaping the response of homeostatic brainstem circuits that receive inputs from higher integrative neuronal centers.",
author = "Browning, {Kirsteen N.} and Travagli, {R. Alberto}",
year = "2007",
month = "8",
day = "22",
doi = "10.1523/JNEUROSCI.1105-07.2007",
language = "English (US)",
volume = "27",
pages = "8979--8988",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "34",

}

TY - JOUR

T1 - Functional organization of presynaptic metabotropic glutamate receptors in vagal brainstem circuits

AU - Browning, Kirsteen N.

AU - Travagli, R. Alberto

PY - 2007/8/22

Y1 - 2007/8/22

N2 - We demonstrated previously that, by suppressing cAMP levels, metabotropic glutamate receptors (mGluRs) play a crucial role in opioid receptor trafficking on GABAergic nerve terminals within gastric brainstem vagal circuits. Using whole-cell patch-clamp recordings, we aimed to correlate the influence of sensory vagal afferent fibers with the functional organization of mGluRs on the synaptic connections between the nucleus tractus solitarius and dorsal motor nucleus of the vagus. Group II mGluRs were identified on both excitatory and inhibitory synapses; the receptor-selective agonist APDC [(2R,4R)-4- aminopyrrolidine-2,4-dicarboxylate] induced a concentration-dependent decrease in glutamatergic and GABAergic synaptic transmission (EC50,∼20 μM for both). The group II mGluRs were activated tonically on GABAergic, but not glutamatergic synapses, as the receptor-selective antagonist (2S)-α-ethylglutamic acid (EGLU; 200 μM) modulated GABA currents only. After selective vagal deafferentation, EGLU was without effect, suggesting that vagal afferent (sensory) fibers are the source of this tonic input. Conversely, group III mGluRs, although not activated tonically, were present on excitatory, but not inhibitory, synapses; in fact, the receptor-selective agonist L-AP-4 [L-(+)-2-amino-4-phosphonbutyric acid] induced a concentration-dependent decrease in glutamatergic synaptic transmission (EC50, ∼2 μM) but had no effect on GABAergic synaptic transmission. Together with our previous results on receptor trafficking, these data suggest that visceral information plays a fundamental role in shaping the response of homeostatic brainstem circuits that receive inputs from higher integrative neuronal centers.

AB - We demonstrated previously that, by suppressing cAMP levels, metabotropic glutamate receptors (mGluRs) play a crucial role in opioid receptor trafficking on GABAergic nerve terminals within gastric brainstem vagal circuits. Using whole-cell patch-clamp recordings, we aimed to correlate the influence of sensory vagal afferent fibers with the functional organization of mGluRs on the synaptic connections between the nucleus tractus solitarius and dorsal motor nucleus of the vagus. Group II mGluRs were identified on both excitatory and inhibitory synapses; the receptor-selective agonist APDC [(2R,4R)-4- aminopyrrolidine-2,4-dicarboxylate] induced a concentration-dependent decrease in glutamatergic and GABAergic synaptic transmission (EC50,∼20 μM for both). The group II mGluRs were activated tonically on GABAergic, but not glutamatergic synapses, as the receptor-selective antagonist (2S)-α-ethylglutamic acid (EGLU; 200 μM) modulated GABA currents only. After selective vagal deafferentation, EGLU was without effect, suggesting that vagal afferent (sensory) fibers are the source of this tonic input. Conversely, group III mGluRs, although not activated tonically, were present on excitatory, but not inhibitory, synapses; in fact, the receptor-selective agonist L-AP-4 [L-(+)-2-amino-4-phosphonbutyric acid] induced a concentration-dependent decrease in glutamatergic synaptic transmission (EC50, ∼2 μM) but had no effect on GABAergic synaptic transmission. Together with our previous results on receptor trafficking, these data suggest that visceral information plays a fundamental role in shaping the response of homeostatic brainstem circuits that receive inputs from higher integrative neuronal centers.

UR - http://www.scopus.com/inward/record.url?scp=34548186742&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548186742&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.1105-07.2007

DO - 10.1523/JNEUROSCI.1105-07.2007

M3 - Article

C2 - 17715335

AN - SCOPUS:34548186742

VL - 27

SP - 8979

EP - 8988

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 34

ER -