Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a superficial folium of the dorsal paraflocculus of high decerebrate rabbits, extracellular unitary spikes were recorded from a Purkinje cell, while two parallel fibre beams impinging onto that Purkinje cell were separately stimulated in the molecular layer. Climbing fibre afferents were stimulated at the contralateral inferior olive. Quisqualate was ionophoretically applied to the dendrite of the Purkinje cell intersecting one of the stimulated parallel fibre beams (test beam). Long-term depression (longer than 45 min) occurred in Purkinje cell responsiveness to the test beam, but not to the other beam (control beam), when quisqualate was applied for 4 min in conjunction with 2 Hz stimulation of climbing fibres. This effect was completely abolished by simultaneous application of a glutamate blocker, kynurenate, during conjunctive quisqualate-climbing fibre stimulation. Application of quisqualate alone caused a small degree of depression in parallel fibre-Purkinje cell transmission. This effect was abolished when spontaneous activity of climbing fibres was blocked by injection of tetrodotoxin or lidocaine to the contralateral inferior olive, and therefore was due to conjunction of quisqualate with spontaneous climbing fibre inputs that normally occurred at 0.5-1.2 Hz. These findings suggest that the occurrence of long-term depression is strictly dependent on conjunction of climbing fibre activity with quisqualate receptor activation.
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PMID:Mode of induction of long-term depression at parallel fibre--Purkinje cell synapses in rabbit cerebellar cortex. 284 11

The effects of quisqualate on primary afferent auditory neurons were examined by comparing the unit activity of guinea pig spiral ganglion neurons before, during, and after the infusion of artificial perilymph containing 1 mM quisqualate into the basal turn scala tympani. In 10 of 13 preparations quisqualate infusion increased unit activity above baseline rates established prior to infusion while control infusions of quisqualate-free artificial perilymph had no appreciable influence on the unit activity of four preparations. Postexcitatory depression typically followed peak evoked excitation, but no purely inhibitory responses were observed. Postexcitatory depression developed into a temporary cessation of spike production in three cases, suggesting depolarization blockade had developed; however, all of these preparations gradually regained some degree of spontaneous unit activity following the termination of quisqualate infusion. Quisqualate-induced excitation may be attributable to the activation of receptors for the afferent neurotransmitter released by hair cells. This interpretation is consistent with our working hypothesis that the primary afferent neurotransmitter is L-glutamate or a structural analog of this excitatory amino acid.
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PMID:Quisqualate excites spiral ganglion neurons of the guinea pig. 391 Jun 31

This study was aimed at clarifying the role of metabotropic glutamate receptors (mGluRs) in the regulation of intracellular Ca2+ concentration ([Ca2+]i in postnatal mouse retinal ganglion neurons (RGNs). RGNs were maintained for 1-2 weeks in vitro by adding brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) to the culture medium. In order to select these cells for electrophysiological measurements, RGNs were vitally labelled with an antibody against Thy-1.2. Voltage-activated Ca2+ currents [ICa(V)] were recorded with patch electrodes in the whole-cell configuration. It was found that racemic +/--1-amino-cyclopentane-trans-1,3-dicarboxylic acid (t-ACPD) or its active enantiomer 1S,3R-ACPD rapidly and reversibly either enhanced or depressed ICa(V). Quisqualate (QA), L-2-amino-4-phosphonobutyrate (L-AP4) and the endogenous transmitter glutamate induced similar effects when ionotropic glutamate receptors were blocked with D-2-amino-5-phosphonovalerate (D-APV) and 6,7-dinitroquinoxaline-2,3-dione (DNQX). omega-Conotoxin GVIA (omega-CgTx GVIA), but not nifedipine prevented modulation of ICa(V) by mGluR agonists. The depression of ICa(V) by t-ACPD was irreversible when cells were dialysed with guanosine-5'-O-(3-thiotriphosphate) (GTP[gamma-S]). Ratio measurements of fura-2 fluorescence in Thy-1+ cells showed that neither t-ACPD, QA nor L-AP4 affected [Ca2+]i by liberation of Ca2+ from intracellular stores. Our results suggest that cultured RGNs express mGluRs. These receptors cannot induce Ca2+ release from intracellular stores but regulate [Ca2+]i by a fast and reversible, G-protein-mediated action on a subpopulation of voltage-activated Ca2+ channels.
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PMID:Potentiating and depressant effects of metabotropic glutamate receptor agonists on high-voltage-activated calcium currents in cultured retinal ganglion neurons from postnatal mice. 790 28

Long-term desensitization of AMPA receptors (LTDA) is a core mechanism of long-term depression, a model of motor learning in the cerebellum. In this study we investigated the expression of neurotrophic factor genes after induction of LTDA in cultured cerebellar slices. LTDA was induced by application of quisqualate and monitored as a population response with a wedge recording technique. The levels of mRNA were quantified by reverse transcription followed by polymerase chain reaction. Quisqualate, at a dose and duration that reliably induced LTDA, elicited a significant and specific increase in BDNF mRNA with a peak at four hours after the application. By cell fractionation, the major source of BDNF mRNA increase was found to be in granule cells. In addition, a small but significant increase of transcripts with specific exon usage was observed in a Purkinje cell fraction. These results indicate that BDNF may be coinduced with LTDA and suggest that the slow and sustained increase of BDNF mRNA might play a role in later phases of synaptic plasticity in the cerebellum.
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PMID:A stimulus paradigm inducing long-term desensitization of AMPA receptors evokes a specific increase in BDNF mRNA in cerebellar slices. 1046

The excitatory responses evoked by glutamate and its agonists in secondary vestibular neurons of the rat were studied during microiontophoretic application of 5-hydroxytryptamine (5-HT). Ejection of 5-HT modified neuronal responsiveness to glutamate in 86% of the studied units, the effect being a depression of the excitatory responses in two-thirds of cases and an enhancement in the remaining third. 5-HT was also effective in modifying 94% of the responses evoked by N-methyl-d-aspartate (NMDA), inducing a depressive effect in 76% of cases and an enhancement in the remaining ones. Quisqualate-evoked effects were depressed and enhanced by 5-HT in about the same number of cases; in contrast, kainate-evoked responses were enhanced. The depressive action of 5-HT was mimicked by application of alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT), a 5-HT(2) receptor agonist, whereas the enhancing effect could be evoked by application of 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT(1A) receptor agonist. The 5-HT(2) receptor antagonist ketanserin was able to reduce, but not to block totally, the depressive action of 5-HT on glutamate- or NMDA-evoked responses. No significant difference was detected between neuronal responses in the lateral and the superior vestibular nucleus. These results indicate that 5-HT is able to modulate the responsiveness of secondary vestibular neurons to excitatory amino acids. Its action is mostly depressive, involves 5-HT(2) receptors, and is exerted on NMDA receptors. A minor involvement of other 5-HT receptors (at least 5-HT(1A)) and other glutamate receptors (for quisqualate and kainate) in the modulatory action of 5-HT is plausible.
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PMID:Influence of serotonin on the glutamate-induced excitations of secondary vestibular neurons in the rat. 1171 69