Synaptic transmission in nucleus tractus solitarius is depressed by Group II and III but not Group I presynaptic metabotropic glutamate receptors in rats

Chao-Yin Chen, Erh Hsin Ling, John M. Horowitz, Ann C. Bonham

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Abstract

Presynaptic metabotropic glutamate receptors (mGluRs) serve as autoreceptors throughout the CNS to inhibit glutamate release and depress glutamatergic transmission. Both presynaptic and postsynaptic mGluRs have been implicated in shaping autonomic signal transmission in the nucleus tractus solitarius (NTS). We sought to test the hypothesis that activation of presynaptic mGluRs depresses neurotransmission between primary autonomic afferent fibres and second-order NTS neurones. In second-order NTS neurones, excitatory postsynaptic currents (EPSCs) synaptically evoked by stimulation of primary sensory afferent fibres in the tractus solitarius (ts) and currents postsynaptically evoked by α-amino-3-hydroxy-4-isoxazoleproprionic acid (AMPA) were studied in the presence and absence of mGluR agonists and antagonists. Real-time quantitative RT-PCR (reverse transcription-polymerase chain reaction) was used to determine whether the genes for the mGluR subtypes were expressed in the cell bodies of the primary autonomic afferent fibres. Agonist activation of Group II and III but not Group I mGluRs reduced the peak amplitude of synaptically (ts) evoked EPSCs in a concentration-dependent manner while having no effect on postsynaptically (AMPA) evoked currents recorded in the same neurones. At the highest concentrations, the Group II agonist, (2S,3S,4S)-CCG/(2S,1′S,2′,S)-2-carboxycyclopropyl (L-CCG-I), decreased the amplitude of the ts-evoked EPSCs by 39 % with an EC50 of 21 μM, and the Group III agonist, L(+)-2-amino-4-phosphonobutyric acid (L-AP4), decreased the evoked EPSCs by 71 % with an EC50 of 1 mM. mRNA for all eight mGluR subtypes was detected in the autonomic afferent fibre cell bodies in the nodose and jugular ganglia. Group II and III antagonists ((2S,3S,4S)-2-methyl-2-(carboxycyclopropyl) glycine (MCCG) and (RS)-α-methylserine-O-phosphate (MSOP)), at concentrations that blocked the respective agonist-induced synaptic depression, attenuated the frequency-dependent synaptic depression associated with increasing frequencies of ts stimulation by 13-34 % and 13-19 %, respectively (P < 0.05, for each). We conclude that Group II and III mGluRs (synthesized in the cell bodies of the primary autonomic afferent fibres and transported to the central terminals in the NTS) contribute to the depression of autonomic signal transmission by attenuating presynaptic release of glutamate.

Original languageEnglish (US)
Pages (from-to)773-786
Number of pages14
JournalJournal of Physiology
Volume538
Issue number3
DOIs
StatePublished - Feb 1 2002

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Metabotropic Glutamate Receptors
Solitary Nucleus
Synaptic Transmission
Excitatory Postsynaptic Potentials
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Neurons
Glutamic Acid
Nodose Ganglion
Autoreceptors
Reverse Transcription
Neck
Polymerase Chain Reaction
Messenger RNA
Acids
Genes
Cell Body

ASJC Scopus subject areas

  • Physiology

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Synaptic transmission in nucleus tractus solitarius is depressed by Group II and III but not Group I presynaptic metabotropic glutamate receptors in rats. / Chen, Chao-Yin; Ling, Erh Hsin; Horowitz, John M.; Bonham, Ann C.

In: Journal of Physiology, Vol. 538, No. 3, 01.02.2002, p. 773-786.

Research output: Contribution to journalArticle

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