Expression of metabotropic glutamate receptor 8 in autonomic cell groups of the medulla oblongata of the rat

doi:10.1016/S0006-8993(02)03619-3

Brain Research

Volume 957, Issue 1, 6 December 2002, Pages 162-173

https://doi.org/10.1016/S0006-8993(02)03619-3 Get rights and content

Abstract

Metabotropic glutamate receptors (mGluRs) in the medulla oblongata have been suggested to have a functional role in the regulation of cardiovascular baroreflexes. The present study examines the localization of mGluR8 autonomic nuclei of the medulla of the rat. mGluR8 immunoreactivity was observed in the cell bodies and/or processes of the dorsolateral, interstitial, medial, intermediate, ventral, ventrolateral, subpostremal, commissural, parvicellular and gelatinosus subnuclei of the nucleus tractus solitarius (NTS). The intensity of mGluR8 staining was highest in the commissural and interstitial subnuclei at the level of the area postrema. Commissural NTS is involved in regulation of baro-, and chemo-reflexes whereas the interstitial nucleus mediates respiratory reflexes. In the area postrema, diffuse staining was observed in the cell bodies, dendrites and fibers of the dorsal and central regions. In vagal outflow nuclei, mGluR8 immunoreactivity was observed in: (1) the cell bodies and processes of the dorsal motor nucleus of the vagus (DMN) throughout the rostro-caudal extent; and (2) the cell bodies and fibers throughout the rostro-caudal extent of the dorsal and ventral division the nucleus ambiguus (NA). Staining in the ventrolateral medulla was restricted to regions ventral to the nucleus ambiguus and dorsal to the lateral reticulate nucleus. The present study is the first to provide a detailed mapping of mGluR8 within the autonomic nucleii of the medulla and suggests that this subtype may be involved in shaping synaptic transmission in these central nuclei.

Introduction

Specific regions of the medulla oblongata mediate central control of baroreflex function. Among these regions is the nucleus tractus solitarius (NTS), which acts as the central terminus for visceral sensory information including baroreceptor and chemoreceptor afferents from the carotid sinus, aortic arch and cardiopulmonary receptors [22], [23], [24], [48]. Integration of this information by the NTS results in the modulation of activity within other regions of the hindbrain involved in regulating autonomic outflow.

l-glutamate is one of the primary neurotransmitters utilized by the NTS and the ventral lateral medulla, and has an important role in cardiovascular function [5], [16], [32], [39], [43], [44]. l-glutamate can bind to either ionotropic glutamate receptors or metabotropic glutamate receptors (mGluRs), which mediate fast excitatory transmission and second messenger-evoked transmission, respectively [4], [9], [11]. Presently, eight mGluR subtypes plus several splice variants have been cloned and are classified into three groups based on amino acid sequence homology, pharmacology and signal transduction mechanism [9], [34]. Group I mGluRs (mGluR1and mGluR5) have been located mainly on postsynaptic nerve terminals. These receptors are sensitive to 3, 5-dihydroxyphenylglycine (DHPG) and are positively coupled to inositol triphosphate production. Group II and group III mGluRs are negatively coupled to adenylate cyclase activity. Group II mGluRs (mGluR2 and mGluR3) are sensitive to 2-(2, 3-dicarboxycyclopropyl)glycine (DCG-IV) and are found on both pre- and postsynaptic terminals. Group III mGluRs (mGluR4, mGluR6, mGluR7) are sensitive to l-aminophosphonoic acid (L-AP4) and are found predominantly on presynaptic terminals [4], [9].

Both in vitro and in vivo studies have demonstrated the ability of mGluRs to modulate cardiovascular function at the level of the NTS [12], [14], [28], [37], while in vivo studies in anesthetized rats have shown that mGluR activation may be involved in the regulation of cardiovascular and respiratory function in the ventrolateral medulla [35], [45], [47]. Recent mRNA expression studies have shown that the NTS expresses the genes encoding all eight mGluR subtypes [21]. In addition, immunocytochemical studies from this lab have shown protein immunoreactivity for mGluR1a, mGluR2/3, mGluR5 and mGluR7 in the NTS and mGluR1a in the ventrolateral medulla [19]. Presently, studies examining localization of mGluR8 in the autonomic regions of the medulla are lacking. Therefore, the purpose of the present study was to describe expression of mGluR8 in medullary nuclei involved in the regulation of baroreflex function, including the subnuclei of the NTS, the area postrema, the vagal preganglionic neurons and the ventral lateral medulla.

Section snippets

Immunocytochemistry

All protocols were approved by the Institutional Animal Care and Use Committee and conform to NIH guidelines. Sprague–Dawley rats (n=6) were anesthetized with halothane, transcardially perfused with 0.1 M phosphate buffered saline (PBS; pH 7.4) followed by 4% paraformaldehyde in PBS. The brainstems were removed, placed overnight in 30% sucrose solution, and 20 μM transverse sections were cut with a cryostat. The sections were immunostained as follows: (1) free-floating sections were rinsed in

Nucleus of the solitary tract

The various subnuclei of the NTS were defined according to the major subdivisions described by Altschuler et al., Loewy and Burton and Herbert et al. [1], [20], [29]. The subdivisions include: central (c), commissural (com), dorsolateral (dl), dorsomedial (dm), gelatinosus (gel), intermedial (int), interstitial (is), medial (m), parvicellular (pc), sub postrema (sp), ventral (v), and ventrolateral (vl). Although metabotropic glutamate receptor 8 (mGluR8) immunoreactivity could be observed in

Discussion

Glutamatergic neurotransmission is an important component of cardiovascular reflex function [31], [44]. Multiple functional studies have demonstrated how mGluRs may potentially modulate synaptic transmission in autonomic regions of the medulla [13], [15], [28], [35], [37], [45], [47] while recent molecular studies demonstrate localization and expression of different mGluR subtypes in these regions [19], [21]. Presently, studies examining the localization of the recently identified group III

Acknowledgements

This work was supported by National Heart, Lung, and Blood Institute Grant HL-59676.

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Research reportExpression of metabotropic glutamate receptor 8 in autonomic cell groups of the medulla oblongata of the rat

Abstract

Introduction

Section snippets

Immunocytochemistry

Nucleus of the solitary tract

Discussion

Acknowledgements

Neurosci. Lett.

Brain Res.

Brain Res. Bull.

Brain Res.

Eur. J. Pharmacol.

Neurosci. Lett.

Brain Res.

J. Autonom. Nerv. Sys.

Neuron

Brain Res.

Brain Res.

Neuropharmacology

Brain Res.

Viscerotopic representation of the upper alimentary tract in the rat: Sensory ganglia and nuclei of the solitary and spinal trigeminal tracts

J. Comp. Neurol.

Viscerotopic representation of the upper alimentary tract in the medulla oblongata in the rat: The nucleus ambiguus

J. Comp. Neurol.

Brainstem viscerotopic organization of afferents and efferents involved in the control of swallowing

Am. J. Med.

Regulation of neurotransmitter release by metabotropic glutamate receptors

J. Neurochem.

Brainstem and bulbospinal neurotransmitter systems in the control of blood pressure

J. Hypertension

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

J. Physiol.

Nucleus ambiguus projections to cardiac ganglia of rat atria: an anterograde tracing study

J. Comp. Neurol.

Pharmacology and functions of metabotropic glutamate receptors

Annu. Rev. Pharm. Toxicol.

Glutamate in the nucleus of the solitary tract activates both ionotropic and metabotropic glutamate receptors

Am. J. Physiol.

Cardiovascular response to group I metabotropic glutamate receptor activation in NTS

Am. J. Physiol.

Activation of metabotropic glutamate receptors produces reciprocal regulation of ionotropic glutamate and GABA responses in the nucleus of the tractus solitarius of the rat

J. Neurosci.

Research report
Expression of metabotropic glutamate receptor 8 in autonomic cell groups of the medulla oblongata of the rat