Pattern-Specific Synaptic Mechanisms in a Multifunctional Network. II. Intrinsic Modulation by Metabotropic Glutamate Receptors

The in vitro respiratory network contained in the transverse brain stem slice of mice simultaneously generates fast (∼15 min-1) and slow (∼0.5 min-1) rhythmic activities corresponding to fictive eupnea (“normal” breathing) and fictive sighs. We show that these two activity patterns are differentially controlled through the modulatory actions of metabotropic glutamate receptors (mGluRs). Sighs were selectively inhibited by agonists of the group III mGluRs according to a pharmacological profile most consistent with activation of mGluR8. Sighs were also blocked by the supposedly inactive L-isomer of the widely used N-methyl-d-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanoic acid (L-AP5, 5 μM), an effect that was abolished in the presence of group III mGluR antagonists. Excitatory postsynaptic potentials (EPSPs) were recorded in pre-Bötzinger Complex neurons after stimulation of the contralateral ventral respiratory group (VRG); evoked EPSP amplitude was variably reduced after bath application of the group III agonist l-serine- O-phospate (L-SOP), with an average reduction of 15%. Therefore although group III mGluRs do play a role in regulating synapse strength, this seems to be only a minor factor in the regulation of synapses made by midline-crossing axons. Intrinsic modulation of the respiratory central pattern generator by mGluRs appears to be an essential component of the multifunctionality that characterizes this network.

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Activation of metabotropic glutamate receptors induces long-term depression of GABAergic inhibition in hippocampus

Journal of Neurophysiology ◽

10.1152/jn.1993.69.3.1000 ◽

1993 ◽

Vol 69 (3) ◽

pp. 1000-1004 ◽

Cited By ~ 67

Author(s):

Y. B. Liu ◽

J. F. Disterhoft ◽

N. T. Slater

Keyword(s):

Glutamate Receptors ◽

Metabotropic Glutamate Receptors ◽

Hippocampal Slices ◽

Input Resistance ◽

Nmda Receptor Antagonist ◽

Metabotropic Glutamate ◽

Epileptiform Discharges ◽

Bath Application

1. The long-term enhancement of synaptic excitability in CA1 hippocampal pyramidal neurons produced by activation of metabotropic glutamate receptors (mGluRs) was studied in rabbit hippocampal slices in vitro. 2. Bath application of the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3- dicarboxylic acid (1S,3R-ACPD) (5-20 microM) for 20 min produced a reversible depolarization of membrane potentiatil, blockade of spike accommodation, and increase in input resistance of CA1 neurons. However, a long-lasting increase in synaptic excitability was observed: single stimuli applied to the Schaffer collateral commisural fiber pathway evoked epileptiform discharges in the presence of 1S,3R-ACPD and after the washout of 1S,3R-ACPD, persistent paroxysmal depolarization shifts (PDSs) were evoked by afferent stimulation. A long-lasting enhancement of synaptic excitability was also observed in the presence of the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5), which blocked the stimulation-evoked PDS and associated afterdischarges. 3. When biphasic, monosynaptically evoked inhibitory post-synaptic potentials (IPSPs) were recorded in the presence of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10–15 microM) and D-AP5 (20 microM), the bath application of 1S,3R-ACPD produced a significant reduction (approximately 50%) of both components of the IPSP, which persisted after the washout of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

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Group III Metabotropic Glutamate Receptors (mGluRs) Modulate Transmission of Gustatory Inputs in the Brain Stem

Journal of Neurophysiology ◽

10.1152/jn.00135.2009 ◽

2009 ◽

Vol 102 (1) ◽

pp. 192-202 ◽

Cited By ~ 4

Author(s):

Robert M. Hallock ◽

Christopher J. Martyniuk ◽

Thomas E. Finger

Keyword(s):

Glutamate Receptors ◽

Metabotropic Glutamate Receptors ◽

Field Potential ◽

Taste System ◽

Group Iii ◽

Metabotropic Glutamate ◽

Group I ◽

Bath Application ◽

Afferent Synapse

Glutamate is the principal neurotransmitter at the primary sensory afferent synapse in the medulla for the taste system. At this synapse, glutamate activates N-methyl-d-aspartate (NMDA) and non-NMDA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA] and kainate) ionotropic receptors to effect a response in the second-order neurons. The current experiment is the first to examine the role of metabotropic glutamate receptors (mGluRs) in the transmission of taste information. In an in vitro slice preparation of the primary vagal gustatory nucleus in goldfish, primary gustatory afferent fibers were stimulated electrically, whereas evoked dendritic field potentials were recorded in the sensory layers. Recordings were made before, during, and after bath application of mGluR agonists for various mGluR groups and subtypes. Whereas l-AP4, a group III agonist, reduced the field potential, group I and group II agonists had no effect. Furthermore, the selective mGluR4 agonist ACPT-III and mGluR8 agonist PPG were effective at reducing the field potential, whereas agonists selective for mGluR6 and 7 were not. MAP4, a group III mGluR antagonist, attenuated frequency-dependent depression, indicating that endogenous glutamate binds to presynaptic mGluRs under normal conditions. Furthermore, polymerase chain reaction showed that mRNA for mGluR4 and 8 is expressed in the vagal ganglia, a prerequisite if those receptors are expressed presynaptically in the vagal lobe. Collectively, these experiments indicate that mGluR4 and 8 are presynaptic at the primary gustatory afferent synapse and that their activation inhibits glutamatergic release.

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Group I Metabotropic Glutamate Receptors Are Differentially Expressed by Two Populations of Olfactory Bulb Granule Cells

Journal of Neurophysiology ◽

10.1152/jn.01202.2006 ◽

2007 ◽

Vol 97 (4) ◽

pp. 3136-3141 ◽

Cited By ~ 8

Author(s):

Thomas Heinbockel ◽

Kathryn A. Hamilton ◽

Matthew Ennis

Keyword(s):

Olfactory Bulb ◽

Glutamate Receptors ◽

Metabotropic Glutamate Receptors ◽

Granule Cells ◽

Mitral Cell ◽

Mitral Cells ◽

Patch Clamp Recording ◽

Metabotropic Glutamate ◽

Group I ◽

Bath Application

In the main olfactory bulb, several populations of granule cells (GCs) can be distinguished based on the soma location either superficially, interspersed with mitral cells within the mitral cell layer (MCL), or deeper, within the GC layer (GCL). Little is known about the physiological properties of superficial GCs (sGCs) versus deep GCs (dGCs). Here, we used patch-clamp recording methods to explore the role of Group I metabotropic glutamate receptors (mGluRs) in regulating the activity of GCs in slices from wildtype and mGluR−/− mutant mice. In wildtype mice, bath application of the selective Group I mGluR agonist DHPG depolarized and increased the firing rate of both GC subtypes. In the presence of blockers of fast synaptic transmission (APV, CNQX, gabazine), DHPG directly depolarized both GC subtypes, although the two GC subtypes responded differentially to DHPG in mGluR1−/− and mGluR5−/− mice. DHPG depolarized sGCs in slices from mGluR5−/− mice, although it had no effect on sGCs in slices from mGluR1−/− mice. By contrast, DHPG depolarized dGCs in slices from mGluR1−/− mice but had no effect on dGCs in slices from mGluR5−/− mice. Previous studies showed that mitral cells express mGluR1 but not mGluR5. The present results therefore suggest that sGCs are more similar to mitral cells than dGCs in terms of mGluR expression.

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Functional interaction between adenosine A2A and group III metabotropic glutamate receptors to reduce parkinsonian symptoms in rats

Neuropharmacology ◽

10.1016/j.neuropharm.2008.06.038 ◽

2008 ◽

Vol 55 (4) ◽

pp. 483-490 ◽

Cited By ~ 28

Author(s):

Sebastien Lopez ◽

Nathalie Turle-Lorenzo ◽

Tom H. Johnston ◽

Jonathan M. Brotchie ◽

Stephan Schann ◽

...

Keyword(s):

Glutamate Receptors ◽

Metabotropic Glutamate Receptors ◽

Functional Interaction ◽

Group Iii ◽

Metabotropic Glutamate ◽

Adenosine A2a

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Metabotropic glutamate receptors switch visual response mode of lateral geniculate nucleus cells from burst to tonic

Journal of Neurophysiology ◽

10.1152/jn.1996.76.3.1800 ◽

1996 ◽

Vol 76 (3) ◽

pp. 1800-1816 ◽

Cited By ~ 62

Author(s):

D. W. Godwin ◽

J. W. Vaughan ◽

S. M. Sherman

Keyword(s):

Glutamate Receptors ◽

Lateral Geniculate Nucleus ◽

Metabotropic Glutamate Receptors ◽

Cell Activity ◽

Response Mode ◽

Visual Response ◽

Relay Cell ◽

Metabotropic Glutamate ◽

Lateral Geniculate

1. Metabotropic glutamate receptors (mGluRs) on relay cells of the lateral geniculate nucleus appear to be activated exclusively by cortical inputs. We thus sought to manipulate these receptors in an effort to gain insight into the possible role of the corticogeniculate pathway. We used in vivo recording and pharmacological techniques in cats to activate or inactivate these receptors on geniculate neurons while analyzing their response properties. 2. Iontophoretic application of the mGluR agonist 1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD) to X and Y cells in the geniculate A laminae diminished or abolished burst activity characteristic of low-threshold Ca2+ spikes. This was accompanied by pronounced changes in the visual response, including a decrease in signal detectability as measured with receiver operating characteristic curves. 3. ACPD effects appear specific to mGluRs, because a specific antagonist of ionotropic glutamate receptors (iGluRs) failed to affect the ACPD-evoked responses, and antagonists of ACPD failed to affect iGluR-mediated responses. We found that 3,5-dihydroxyphenylglycine, an agonist reported to be specific for phosphatidylinositol (PI)-linked mGluRs, had effects similar to those of ACPD, implying that these effects are mediated by PI-coupled mGluRs. Furthermore, antagonists reported to be effective against PI-linked mGluRs were effective in antagonizing the ACPD-mediated effects, and substances reported to be agonists to mGluRs coupled to the adenosine 3',5'-cyclic monophosphate cascade did not affect neuronal responses on their own. These data, when added to our preliminary anatomic data, indicate that the receptor responsible for the observed effects may be mGluR1, or a functionally equivalent mGluR. 4. Activation of mGluRs produces changes in geniculate relay cell activity consistent with depolarization of these cells seen during in vitro studies. Such membrane depolarization has been shown to control the activation state of a voltage-dependent Ca2+ conductance, and this, in turn, determines whether the relay cell fires in tonic or burst mode. Our data show that application of ACPD produces a shift in response mode from burst to tonic. Because response mode is an important characteristic of the geniculate relay and because the activation state of certain mGluRs, which helps determine response mode may be controlled by corticogeniculate input, we conclude that an important function of this input is to provide a visuotopically discrete transition from burst to tonic response mode.

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