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

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.

Group I Metabotropic Glutamate Receptors on Second-Order Baroreceptor Neurons Are Tonically Activated and Induce a Na+–Ca2+Exchange Current

“…As in previous studies ( Chen et al 2002Chen et al , 2004) the brain was rapidly exposed and submerged in ice-cold (Ͻ4°C) high-sucrose artificial cerebrospinal fluid (aCSF) that contained (in mM): 3 KCl, 2 MgCl 2 , 1.25 NaH 2 PO 4 , 26 NaHCO 3 , 10 glucose, 220 sucrose, and 2 CaCl 2 (300 mosmol kg Ϫ1 ); the pH was 7.4 when continuously bubbled with 95% O 2 -5% CO 2 . Brain stem coronal slices (250 m thick) containing the intermediate to caudal NTS and the tractus solitarius (TS) were cut with a Vibratome 1000 (Technical Products International, St. Louis, MO).…”

“…As previously described (Chen et al 2002(Chen et al , 2004, 4-to 5-mm segments of both aortic depressor nerves (ADNs) were carefully isolated and placed on a section of parafilm for application of the crystal form of the fluorescent tracer, 1,1Ј-dilinoleyl-3,3,3Ј,3Ј tetra-methylindocarbo-cyanine, 4-chlorobenzenesulfonate [FAST DiI solid; DiI ⌬ 9,12 -C 18 (3)] on these nerves and coated with polyvinylsiloxane gel. DiI is transported anterogradely to label the terminal boutons, without being transported transynaptically.…”

“…DiI is transported anterogradely to label the terminal boutons, without being transported transynaptically. To allow for transport of the dye to the terminal boutons, the rats were allowed to recover for 2 wk before the experimental protocols were performed (Chen et al 2002(Chen et al , 2004). …”

“…Hay et al (1999) described the expression of four mGluR subtypes (mGluR1a, mGluR2/3, mGluR5, and mGluR7) within specific NTS subnuclei. However, the functional characterization of mGluRs in baroreceptor signal processing in the NTS has focused largely on Group II and III mGluRs, which suppress baroreceptor signal transmission by limiting glutamate release from primary baroreceptor afferent fibers (Chen et al 2002;Liu et al 1998) and Group II mGluRs to decrease ␥-aminobutyric acid (GABA) release (Chen and Bonham 2004). The role of the postsynaptic mGluRs in regulating baroreceptor signaling in the NTS is poorly understood.…”

Prostaglandin E2 depresses solitary tract-mediated synaptic transmission in the nucleus tractus solitarius

“…Jitter was calculated as the shock-to-shock variability in the onset latency. An onset latency variability of < 0.5 ms was taken as evidence for a putative monosynaptic response (Chen et al 2002). Paired-pulse ratio is defined as the ratio of the second evEPSC peak amplitude divided by the first evEPSC peak amplitude using a 20 ms interpulse interval.…”