UMLS:C0011570 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0011570 (depression)
172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ventral septal area (VSA) is considered to be critically involved in the control of the height and duration of fever. The major excitatory input to this region of the brain is glutamatergic, and the aim of this study was to investigate possible modulation of this synapse by metabotropic glutamate (mGlu) receptors. Whole-cell patch recordings were made from individual VSA neurons voltage-clamped at -60 mV. Activation of either group I or group II mGlu receptors (by bath application of 3,5-dihydroxyphenylglycine (DHPG) or (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV), respectively) produced a long-lasting depression of synaptic transmission which in both cases was insensitive to the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonopentanoate (D-AP5). In contrast, application of (S)-2-amino-4-phosphonobutyric acid (L-AP4), a group III mGlu receptor agonist, had a biphasic effect on synaptic transmission in the VSA, first eliciting a transient depression of transmission during drug application, followed by a marked and sustained potentiation of synaptic transmission upon drug washout. The response elicited by L-AP4 was dependent on NMDA receptor activation, as in the presence of D-AP5 the potentiation was replaced by an underlying long-term depression (LTD) of transmission. These data provide the first evidence that metabotropic glutamate receptor agonists can induce both NMDA receptor-dependent and -independent modulation of synaptic transmission in the VSA.
...
PMID:Modulation of synaptic transmission in the rat ventral septal area by the pharmacological activation of metabotropic glutamate receptors. 1079 61

Hippocampal long-term depression (LTD) involves a long-lasting decrease in synaptic transmission which is induced by low-frequency stimulation (LFS). Evidence exists that variability in the responsiveness of rat strains to LFS occurs. Thus, Wistar rats readily express LTD in vivo, whereas Hooded Lister rats demonstrate at best short-term depression (STD) in response to LFS. Group III metabotropic glutamate receptor (mGluR)-involvement in the induction of LTD in freely moving rats has not yet been investigated. This study therefore examined the effect of group III mGluR activation and inhibition on LTD expression, and evaluated these effects in Wistar and Hooded Lister rats. Animals were chronically implanted with recording and bipolar stimulating electrodes in the CA1 region, and an injection cannula in the lateral cerebral ventricle. LFS (1 Hz, 900 pulses) induced LTD in Wistar, and STD in Hooded Lister rats. Agonist priming with L-2-amino-4-phosphonobutanoic acid (AP4, 400 nmol/5 microl) facilitated LTD expression in Hooded Lister but not Wistar rats. The antagonist (RS)-alpha-cyclopropyl-4-phosphonophenylglycine inhibited the facilitatory effects of AP4 in Hooded Lister- and impaired LTD expression in Wistar rats. These data imply a role for group III mGluRs in hippocampal LTD in vivo, and suggest that differences in this mGluR system may account, in part, for strain-dependent variations in LTD expression.
...
PMID:Group III metabotropic glutamate receptors modulate long-term depression in the hippocampal CA1 region of two rat strains in vivo. 1096 39

The aims of this study were, to use agonists selective for the 3 mGlu receptor groups to identify developmental changes in their effects, and to assess the usefulness of proposed selective antagonists as pharmacological tools. Hippocampal slices (400 microm) were prepared from neonate (9 - 14 days) and young adult (5 - 7 weeks) Sprague-Dawley rats. Field excitatory postsynaptic potentials (fEPSP) were recorded from CA1. DHPG (100 microM), a group I agonist, produced a slowly developing enhancement of fEPSP slope in slices from adults. In slices from neonates, DHPG (75 microM) depressed fEPSP slope. DCG-IV (500 nM), a group II agonist, did not affect the fEPSP recorded from slices from adults whereas perfusion in neonate slices produced a sustained depression. The group III agonist L-AP4 (50 microM) was ineffective in adult slices but depressed fEPSP slope in slices prepared from neonates. DHPG-induced depression of fEPSP slope was inhibited by 4-CPG (400 microM), a group I antagonist, but was unaffected by MCCG (500 microM) and MAP4 (500 microM), group II and III receptor antagonists respectively. MCCG but not MAP4 antagonized the effects of DCG-IV with 4-CPG producing variable effects. The effect of L-AP4 was unaffected by MCCG, blocked by MAP4, and enhanced by 4-CPG. The results show that the effects of the agonists for all groups of mGlu receptors are developmentally regulated. Furthermore, MCCG and MAP4 behave as effective and selective antagonists for group II and group III mGlu receptors respectively, whereas the usefulness of 4-CPG as a group I antagonist may be limited.
...
PMID:Developmental regulation of hippocampal excitatory synaptic transmission by metabotropic glutamate receptors. 1101 95

Effects of metabotropic glutamate receptors of the duration of posttetanic changes in monosynaptic excitatory postsynaptic potentials (mEPSP), evoked by afferent and reticulospinal input stimulation, were investigated in lumbar motoneurons of the frog isolated spinal cord. It was found that application of MAP4 (25 microM), a selective antagonist of group III of these receptors, prolonged posttetanic potentiation and depression of synaptic transmission, whereas activation of this group of metabotropic glutamate receptors by L-AP4 (1 mM), a selective agonist of these receptors, suppressed the amplitude of synaptic responses, but did not affect the dynamics of development of posttetanic changes. The NMDA receptor antagonist AP5 (50 microM), added to the perfusing solution, blocked completely the effects produced by MAP4. Neither selective antagonist MCCG (400 microM), nor agonist tACPD (50 microM) of group II metabotropic glutamate receptors affected the terms of mEPSP posttetanic potentiation and depression, although the latter, in contrast to the antagonist, in most cases increased the synaptic potential amplitude. The data obtained permit to suggest that group III metabotropic receptors may control the duration of posttetanic changes of synaptic transmission in the frog spinal motoneurons. The long-term changes in the investigated synapses seem to be mediated by activation of postsynaptic metabotropic glutamate receptors (most likely, of group I receptors), which is normally masked with activation of group III presynaptic autoreceptors. The mechanism of such an induction essentially depends on activation of NMDA type of inotropic glutamate receptors.
...
PMID:[The effect of metabotropic glutamate receptors on longitude of posttetanic reaction in spinal motoneurons of frog]. 1139 19

The actions of reportedly group-selective metabotropic glutamate (mGlu) receptor agonists and antagonists on neurotransmission at parallel fibre-Purkinje cell synapses in the rat cerebellum have been characterised using sharp microelectrode recording and an in vitro slice preparation. Application of the group I agonist (S)-3,5-dihydroxyphenylglycine (DHPG) or the group III selective agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) depressed synaptic transmission in a reversible and concentration-dependent manner (EC(50)=18 and 5 microM, respectively). The depression produced by DHPG was unrelated to the depolarisation observed in some Purkinje cells. The group II agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV, 1 microM) had no effect. The effects of DHPG were inhibited by the group I-selective antagonist 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt), but not by the group II/III antagonist alpha-methyl-4-phosphonophenylglycine (MPPG). The effect of L-AP4 was inhibited by MPPG, but not by the group I/II antagonist (S)-alpha-methyl-4-carboxyphenylglycine (MCPG). By themselves, the antagonists did not affect the EPSPs, suggesting that neither receptor is activated during low frequency neurotransmission. It is concluded that, in addition to the excitatory role for group I receptors described previously, both group I and III (but not group II) mGlu receptors operate at this synapse to inhibit synaptic transmission. The specific receptor subtypes involved are likely to be mGlu1 and mGlu4.
...
PMID:Metabotropic glutamate receptor subtypes modulating neurotransmission at parallel fibre-Purkinje cell synapses in rat cerebellum. 1144 84

The purpose of this chapter is to review some of the recent progress in the understanding of the cellular and biophysical mechanisms that are involved in the regulation of arterial baroreceptor neurotransmission. Synaptic depression or fatigue following repeated neuronal stimulation has been shown at central baroreceptor synapses in vivo and in vitro. As most of the central neurons have a limited number of vesicles, vesicle retrieval or endocytosis following exocytosis is thought to play a major role in preserving synaptic transmission. We have hypothesized that central baroreceptor terminals may inhibit their own synaptic transmission via feedback activation of presynaptic metabotropic glutamate receptors (mGluRs). We have analyzed the effects of mGluR autoreceptors (group III mGluRs) on voltage-gated calcium channels using standard patch-clamp techniques and on the process of exocytosis and endocytosis in aortic baroreceptor neurons using the quantitative imaging dye FM1-43 and FM2-10. Usng the whole-cell patch-clamp technique, we have found that activation of group III mGluRs with L-AP4 inhibits peak calcium channel current. Furthermore, activation of group III mGluRs with L-AP4 markedly decreases stimulation-induced exocytosis in aortic baroreceptor neurons, as measured with FM1-43, and inhibits synapsin I phosphorylation. These results suggest that activation of group III mGluRs may inhibit synaptic transmission by (1) inhibiting calcium influx, (2) decreasing synaptic vesicle exocytosis, and (3) modulating the mechanisms governing synaptic vesicle recovery and endocytosis. These effects of mGluRs on baroreceptor synaptic vesicles may contribute to the baroreceptor/nucleus tractus solitarius synaptic depression observed in vivo.
...
PMID:Cellular mechanisms regulating synaptic vesicle exocytosis and endocytosis in aortic baroreceptor neurons. 1145 71

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 alpha-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 microM, 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)-alpha-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.
...
PMID:Synaptic transmission in nucleus tractus solitarius is depressed by Group II and III but not Group I presynaptic metabotropic glutamate receptors in rats. 1182 64

Group III metabotropic glutamate receptors (mGluRs) are selectively activated by L-2-amino-4-phosphonobutyrate (L-AP4), which produces depression of synaptic transmission. The relative contribution of different group III mGluRs to the effects of L-AP4 remains to be clarified. Here, we assessed the distribution of mGluR4 in the rat and mouse brain using affinity-purified antibodies raised against its entire C-terminal domain. The antibodies reacted specifically with mGluR4 and not with other mGluRs in transfected COS 7 cells. No immunoreactivity was detected in brains of mice with gene-targeted deletion of mGluR4. Pre-embedding immunocytochemistry for light and electron microscopy showed the most intense labelling in the cerebellar cortex, basal ganglia, the sensory relay nuclei of the thalamus, and some hippocampal areas. Immunolabelling was most intense in presynaptic active zones. In the basal ganglia, both the direct and indirect striatal output pathways showed immunolabelled terminals forming mostly type II synapses on dendritic shafts. The localisation of mGluR4 on GABAergic terminals of striatal projection neurones suggests a role as a presynaptic heteroreceptor. In the cerebellar cortex and hippocampus, mGluR4 was also localised in terminals establishing type I synapses, where it probably operates as an autoreceptor. In the hippocampus, mGluR4 labelling was prominent in the dentate molecular layer and CA1-3 strata lacunosum moleculare and oriens. Somatodendritic profiles of some stratum oriens/alveus interneurones were richly decorated with mGluR4-labelled axon terminals making either type I or II synapses. This differential localisation suggests a regulation of synaptic transmission via a target cell-dependent synaptic segregation of mGluR4. Our results demonstrate that, like other group III mGluRs, presynaptic mGluR4 is highly enriched in the active zone of boutons innervating specific classes of neurones. In addition, the question of alternatively spliced mGluR4 isoforms is discussed.
...
PMID:Distribution and synaptic localisation of the metabotropic glutamate receptor 4 (mGluR4) in the rodent CNS. 1190 82

Modulation of short-term plasticity by activation of group III metabotropic glutamate receptors (mGluR) was investigated in the lateral perforant path of the dentate gyrus of the rat hippocampus in vitro. Brief trains of stimulation (10 stimuli at 1-100 Hz) evoked short-term depression of field excitatory postsynaptic potentials (EPSPs), with a steady-state level of short-term depression being attained after approximately 5 stimuli. The steady-state level of depression was frequency-dependent, increasing linearly between 1 and 200 Hz. The curve relating transmitter release per unit time to frequency of stimulation increased linearly up to a limiting frequency of 20-50 Hz, and then flattened at higher frequencies. Activation of group III mGluR by the selective agonist L-(+)-2-amino-4-phosphonobutyric acid (L-AP4) had two distinct actions. Firstly, the test EPSP evoked at low test frequencies was inhibited, and secondly, short-term depression evoked at high frequencies was reduced in a frequency and agonist concentration-dependent manner. Short-term facilitation became prominent at high stimulation frequencies as short-term depression was inhibited by activation of group III mGluR. Activation of group III mGluR also shifted the limiting frequency to higher values.
...
PMID:Presynaptic group III mGluR modulation of short-term plasticity in the lateral perforant path of the dentate gyrus in vitro. 1236 2

1. Group III metabotropic glutamate receptors (mGluRs) of the subtype 4a are localized within presynaptic active zones of cerebellar parallel fibre (PF)-Purkinje cell (PC) synapses. In order to investigate the conditions necessary for group III mGluR autoreceptor-activation by synaptically released glutamate, we characterized the effects of selective agonists and antagonists on excitatory postsynaptic currents (EPSCs) evoked by several distinct PF stimulation patterns. 2. The group III mGluR-selective agonist L-AP4 depressed evoked EPSCs at PF-PC synapses in rat brain slices with an EC(50) of 2.4 microM and maximum inhibition of 80%. This L-AP4-induced depression was antagonized by the group III mGluR-selective antagonist MSOP with an estimated equilibrium dissaciation constant of 12.5 microM. 3. Paired-pulse or four-pulse PF stimulations did not activate presynaptic group III mGluRs as revealed by the lack of effect of 1 mM MSOP on relative test EPSC amplitudes with latencies of 250-500 ms. The potentiation of a test EPSC evoked 200-500 ms after a short tetanic burst (100 Hz for 60 ms), was also unchanged in the presence of MSOP. 4. Endogenous autoreceptor-activation was revealed only during prolonged stimulation trains (10 Hz for 4.4 s), where, in the presence of 1 mM MSOP, the EPSC amplitudes were enhanced by 15%. 5. These observations support an autoreceptor function of group III mGluRs and a role in short-term synaptic plasticity at PF synapses. However, the low to moderate activation levels observed, despite the close spatial relation with glutamate release sites, suggests that additional mechanisms regulate receptor activation.
...
PMID:Group III metabotropic glutamate receptors as autoreceptors in the cerebellar cortex. 1259 15

<< Previous 1 2 3 4 5 6 7 Next >>