Functional organization of presynaptic metabotropic glutamate receptors in vagal brainstem circuits.
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, approximately 20 microM for both). The group II mGluRs were activated tonically on GABAergic, but not glutamatergic synapses, as the receptor-selective antagonist (2S)-alpha-ethylglutamic acid (EGLU; 200 microM) 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, approximately 2 microM) 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.
Browning
Kirsteen N
KN
Department of Neuroscience, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana 70808, USA.
Travagli
R Alberto
RA
D000596:Amino Acids; D000818:Animals; D000831:Animals, Newborn; D001933:Brain Stem / Q000166:cytology* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D041981:Gastrointestinal Tract / Q000294:innervation; D005971:Glutamates / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000166:cytology*; D018408:Patch-Clamp Techniques / Q000379:methods; D017729:Presynaptic Terminals / Q000502:physiology*; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D014628:Vagotomy / Q000379:methods; D014630:Vagus Nerve / Q000502:physiology*
C097299:4-aminopyrrolidine-2,4-dicarboxylic acid; D000596:Amino Acids; D005971:Glutamates; D018094:Receptors, Metabotropic Glutamate; C098463:dolaisoleucine; C108822:metabotropic glutamate receptor 2; C017302:alpha-ethylglutamic acid; D011392:Proline
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