NMDA receptors control vagal afferent excitability in the nucleus of the solitary tract

Abstract Previous behavioral studies have demonstrated that presynaptic N-methyl- d -aspartate (NMDA) receptors expressed on vagal afferent terminals are involved in food intake and satiety. Therefore, using in vitro live cell calcium imaging of prelabeled rat hindbrain slices, we characterized whic...

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Bibliographic Details
Published in:Brain research 2015-01, Vol.1595, p.84-91
Main Authors: Vance, Katie M, Rogers, Richard C, Hermann, Gerlinda E
Format: Article
Language:English
Subjects:
2-Amino-5-phosphonovalerate - pharmacology
Adenosine Triphosphate - pharmacology
Afferent Pathways - physiology
Animals
Aspartic Acid - pharmacology
Benzimidazoles - pharmacology
Calcium - metabolism
Calcium imaging
Excitatory Amino Acid Antagonists - pharmacology
GluN2B
GluN2C
GluN2D
In Vitro Techniques
Neurology
NST
Piperidines - pharmacology
Pregnenolone - pharmacology
Presynaptic
Rats
Rats, Long-Evans
Receptors, N-Methyl-D-Aspartate - physiology
Solitary Nucleus - drug effects
Solitary Nucleus - physiology
Sulfonamides - pharmacology
Vagus Nerve - physiology
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Summary:Abstract Previous behavioral studies have demonstrated that presynaptic N-methyl- d -aspartate (NMDA) receptors expressed on vagal afferent terminals are involved in food intake and satiety. Therefore, using in vitro live cell calcium imaging of prelabeled rat hindbrain slices, we characterized which NMDA receptor GluN2 subunits may regulate vagal afferent activity. The nonselective NMDA receptor antagonist d , l -2-amino-5-phosphonopentanoic acid ( d , l -AP5) significantly inhibited vagal terminal calcium influx, while the excitatory amino acid reuptake inhibitor d , l -threo-β-benzyloxyaspartic acid (TBOA), significantly increased terminal calcium levels following pharmacological stimulation with ATP. Subunit-specific NMDA receptor antagonists and potentiators were used to identify which GluN2 subunits mediate the NMDA receptor response on the vagal afferent terminals. The GluN2B-selective antagonist, ifenprodil, selectively reduced vagal calcium influx with stimulation compared to the time control. The GluN2A-selective antagonist, 3-chloro-4-fluoro-N-[4-[[2-(phenylcarbonyl)hydrazino]carbonyl] benzyl]benzenesulfonamide (TCN 201) produced smaller but not statistically significant effects. Furthermore, the GluN2A/B-selective potentiator (pregnenolone sulfate) and the GluN2C/D-selective potentiator [(3-chlorophenyl)(6,7-dimethoxy-1-((4-methoxyphenoxy)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone; (CIQ)] enhanced vagal afferent calcium influx during stimulation. These data suggest that presynaptic NMDA receptors with GluN2B, GluN2C, and GluN2D subunits may predominantly control vagal afferent excitability in the nucleus of the solitary tract.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2014.11.010