Metabotropic glutamate receptors depress vagal and aortic baroreceptor signal transmission in the NTS

Abstract

We sought to determine whether metabotropic glutamate receptors contribute to frequency-dependent depression of vagal and aortic baroreceptor signal transmission in the nucleus of the solitary tract (NTS) in vivo. In α-chloralose-anesthetized rabbits, we determined the number of extracellular action potentials synaptically evoked by low (1 Hz)- or high-frequency vagal (3–20 Hz) or aortic depressor nerve (ADN) (6–80 Hz) stimulation and postsynaptically evoked by the ionotropic glutamate receptor agonist α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). The metabotropic glutamate receptor agonist (2 S,1′ S,2′ S)-2-(carboxycyclopropyl)glycine (L-CCG-I) attenuated NTS responses monosynaptically evoked by 1-Hz vagus stimulation by 34% ( n = 25; P = 0.011), while augmenting AMPA-evoked responses by 64% ( n = 17; P = 0.026). The metabotropic glutamate receptor antagonist α-methyl-4-phosphonophenylglycine (MPPG) did not affect NTS responses to low-frequency vagal stimulation ( n = 11) or AMPA ( n = 10) but augmented responses to high-frequency stimulation by 50% ( n= 25; P = 0.0001). MPPG also augmented NTS responses to high-frequency ADN stimulation by 35% ( n = 9; P = 0.048) but did not affect responses to low-frequency stimulation ( n = 9) or AMPA ( n = 7). The results suggest that metabotropic glutamate receptors, presumably at presynaptic sites, contribute to frequency-dependent depression of vagal and aortic baroreceptor signal transmission in NTS.

Cranial Afferent Glutamate Heterosynaptically Modulates GABA Release onto Second-Order Neurons via Distinctly Segregated Metabotropic Glutamate Receptors

“…Our results add powerful interactions between glutamatergic afferent drive and GABAergic feedback. Because broad-spectrum mGluR antagonists increase NTS activity during vagal and aortic baroreceptor afferent activation (Liu et al, 1998), understanding the interactions between glutamatergic and GABAergic transmission will depend on the unraveling of specific interrelations between distinct subsets of neurons to define their integrative properties.…”

“…ST afferent synaptic transmission substantially depresses at moderate frequencies (Andresen and Yang, 1995). Frequencydependent depression in NTS with cranial afferent activation is reduced by mGluR blockade (Liu et al, 1998). Early work in NTS (Feldman and Felder, 1991) suggested complex interactions between afferent activation and GABA with mGluR participation in regulating ST-evoked responses (Glaum et al, 1993).…”

A Novel Postsynaptic Group II Metabotropic Glutamate Receptor Role in Modulating Baroreceptor Signal Transmission

“…In the NTS glutamate binding to Group II and III mGluRs inhibits baroreceptor signal transmission by limiting glutamate release from the primary baroreceptor afferent fibers (Chen et al, 2002;Liu et al, 1998). Group II mGluRs can also increase baroreceptor signal transmission by decreasing γ-aminobutyric acid (GABA) release at the first central baroreceptor synapses (Chen and Bonham, 2005).…”

Glutamatergic neurotransmission in the nucleus tractus solitarii: Structural and functional characteristics

“…However, electrophysiological recordings indicate that both group II and group III mGluRs are presynaptic autoreceptors that inhibit glutamate release from primary afferent terminals and contribute to the frequencydependent depression of responses evoked by solitary tract stimulation in vitro . Consistent with these results, in vivo experiments indicate that mGluRs within the NTS mediate frequency-dependent depression of vagal and aortic baroreceptor signal transmission (Liu et al, 1998). Group II and group III autoreceptors are present not only on primary afferent terminals but also on terminals from some glutamatergic NTS interneurons, especially those involved in transmitting excitation to gastric-projecting vagal motor neurons (Browning and Travagli, 2007).…”