UMLS:C0011570 - FACTA Search

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

Patches excised from fields CA1 and CA3 of the hippocampus were used to study AMPA receptor responses to repetitive application of brief pulses of agonist. AMPA receptors in field CA1 exhibited a larger degree of paired-pulse depression and a slower recovery rate from desensitization than those from CA3 patches. Responses became progressively smaller during a train of short pulses (4 at 100 Hz), an effect that was greater in CA1 than CA3 patches and that was blocked by a drug (cyclothiazide) that slows desensitization. Cyclothiazide also increased steady state currents during a long pulse of glutamate and had a lower EC50 for CA3 than CA1 AMPA receptors. These results suggest (i) that differences in the relative balance of flip vs. flop subunits affect the kinetic and pharmacological properties of AMPA receptors in vivo, and (ii) that the rate of recovery from desensitization may influence responses to the bursts of afferent activity commonly used to induce long-term potentiation.
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PMID:Response to repetitive stimulation of AMPA receptors in patches excised from fields CA1 and CA3 of the hippocampus. 873 40

The contribution of the substantia nigra (SN) in the positive interaction between dopamine D1 receptor agonists and glutamate antagonists was studied in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of dopaminergic nigro-striatal pathway. Local infusion into the SN of the 6-OHDA lesioned side of NMDA glutamate antagonists MK 801 and CPP or the AMPA antagonist NBQX at doses inducing none or minimal behavioral effects, significantly increased the turning behavior and the expression of c-fos induced, in the lesioned caudate-putamen (CPu), by a parenteral administration of SKF 38393. High doses of MK 801 or CPP infused into the SN produced intense contralateral turning per-se but induced only sparse c-fos expression in the lesioned CPu. The results show that a depression of SN pars reticulata efferent neurons, potentiates D1-mediated responses and suggest that this area may play a role in the positive interaction between glutamate antagonists and D1 receptor agonists.
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PMID:Intranigral injections of glutamate antagonists modulate dopamine D1-mediated turning behavior and striatal c-fos expression. 874 12

To determine physiological roles of metabotropic glutamate receptors (mGluRs) affecting breathing, we examined the effects of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) on synaptic transmission and excitability of phrenic motoneurons (PMNs) in an in vitro neonatal rat brainstem/spinal cord preparation. The effects of 1S,3R-ACPD were multiple, including reduction of inspiratory-modulated synaptic currents and increase of neuronal excitability via an inward current (Iacpd) associated with a decrease of membrane conductance. The mechanism underlying synaptic depression was examined. We found that 1S,3R-ACPD reduced the frequency but not the amplitude of miniature excitatory postsynaptic currents. The current induced by exogenous AMPA was not significantly affected by 1S,3R-ACPD. These results suggest that 1S,3R-ACPD-induced reduction of inspiratory synaptic currents is mediated by presynaptic mGluRs. We also examined the ionic basis for Iacpd. We found that Iacpd had a reversal potential of approximately -100 mV, close to the estimated, EK+ (-95 mV). Elevating extracellular [K+] to 9 mM reduced the Iacpd reversal potential to -75 mV. The K+ channel blocker Ba2+ induced an inward current with a reversal potential at -93 mV associated with a decrease of membrane conductance, closely resembling the effect of 1S,3R-ACPD. Moreover, Ba2+, occluded 1S,3R-ACPD effects. In the presence of Ba2+, Iacpd and the 1S,3R-ACPD-induced decrease of membrane conductance were diminished. Our data indicate that the dominant component of Iacpd results from the blockade of a Ba(2+)-sensitive resting K+ conductance. We conclude that the activation of mGluRs affects the inspiratory-modulated activity of PMNs via distinct mechanisms at pre- and postsynaptic sites.
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PMID:Multiple actions of 1S,3R-ACPD in modulating endogenous synaptic transmission to spinal respiratory motoneurons. 875 28

Cultured hippocampal slices retain many in vivo features with regard to circuitry, synaptic plasticity, and pathological responsiveness, while remaining accessible to a variety of experimental manipulations. The present study used ligand binding, immunostaining, and in situ hybridization assays to determine the stability of AMPA- and NMDA-type glutamate receptors and other synaptic proteins in slice cultures obtained from 11 day postnatal rats and maintained in culture for at least 4 weeks. Binding of the glutamate receptor ligands [3H]AMPA and [3H]MK-801 exhibited a small and transient decrease immediately after slice preparation, but the binding levels recovered by culture day (CD) 5-10 and remained stable for at least 30 days in culture. Autoradiographic analyses with both ligands revealed labeling of dendritic fields similar to adult tissue. In addition, slices at CD 10-20 expressed a low to high affinity [3H]AMPA binding ratio that was comparable with that in the adult hippocampus (10:1). AMPA receptor subunits GluR1 and GluR2/3 and an NMDA receptor subunit (NMDAR1) exhibited similar postcutting decreases as that exhibited by the ligand binding levels, followed by stable recovery. The GluR4 AMPA receptor subunit was not evident during the first 10 CDs but slowly reached detectable levels thereafter in some slices. Immunocytochemistry and in situ hybridization techniques revealed adult-like labeling of subunit proteins in dendritic processes and their mRNAs in neuronal cell body layers. Long-term maintenance was evident for other synapse-related proteins, including synaptophysin, neural cell adhesion molecule isoforms (NCAMs), and an AMPA receptor related antigen (GR53), as well as for certain structural and cytoskeletal components (e.g., myelin basic protein, spectrin, microtubule-associated proteins). In summary, following an initial and brief depression, many synaptic components were expressed at steady-state levels in long-term hippocampal slices, thus allowing the use of such a culture system for investigations into mechanisms of brain synapses.
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PMID:Stable maintenance of glutamate receptors and other synaptic components in long-term hippocampal slices. 877 55

Effects of glutamate and agonists (aspartate, NMDA, quisqualate, AMPA, kainate) on dorsal root and reticulomotoneuronal excitatory postsynaptic potentials (EPSPs), as well as on spontaneous postsynaptic potentials (PSP), were studied in the motoneurons of isolated frog spinal cord. Depolarizing responses were evoked by glutamate or agonists bath application. Amplitude of the response decreased in conditions of TTX-block or replacement of Ca2+ by Mn2+, Mg2+ or Co2+ in perfusing solution. Excitatory amino acid antagonists (kynurenate, CNQX, APV, argiopine) also reduced depolarizing response amplitude. DR and RF EPSPs significantly increased in amplitude (and spontaneous PSP in amplitude and frequency) during depolarization, evoked by glutamate or agonists. The potentiation reached up to 300 %. Potentiation diminished with depolarization decay. Sometimes several minutes depression of EPSPs was observed after the depolarizing response. There was no potentiation of the spontaneous PSPs in conditions of TTX-block or replacement of Ca2+ by Mn2+ in perfusing solution. The data obtained suggest rather presynaptic, than postsynaptic mechanism of the potentiation. We found no depressant effect of glutamate or agonists on postsynaptic glutamate receptors, at least for 10 minutes contact. Effects of more prolonged applications and some changes of EPSP amplitude after depolarizing response appear to be associated with other types of glutamate receptors.
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PMID:[The potentiation of postsynaptic potentials under the influence of glutamate and agonists in the motoneurons of the frog Rana ridibunda]. 877 84

We have addressed the expression of long-term potentiation (LTP) in hippocampal CA1 by comparing AMPA and NMDA receptor-(AMPAR- and NMDAR-) mediated postsynaptic signals. We find that potentiation of NMDAR-mediated signals accompanies LTP of AMPAR-mediated signals, and is associated with a change in variability implying an increase in quantal content. Further, tetanic LTP of NMDAR-mediated signals can be elicited when LTP of AMPAR-mediated signals is prevented. We propose that LTP is mainly expressed presynaptically, and that, while AMPARs respond only to glutamate from immediately apposed terminals, NMDARs also sense glutamate released from terminals presynaptic to neighboring cells. We also find that tetanic LTP increases the rate of depression of NMDAR-mediated signals by the use-dependent blocker MK-801, implying an increase in the glutamate release probability. These findings argue for a presynaptic contribution to LTP and for extrasynaptic spill-over of glutamate onto NMDARs.
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PMID:LTP of AMPA and NMDA receptor-mediated signals: evidence for presynaptic expression and extrasynaptic glutamate spill-over. 881 9

A number of different factors contributed to the rationale for providing a critical review of the field of excitatory amino acids in the cerebral cortex at this time. In addition to the recent growing realisation by clinicians that the excitatory amino acids are linked critically to a number of neurological conditions, including neurodegenerative syndromes such as Alzheimer's disease, cortical damage due to stroke and cerebral ischemia, epilepsy, amyotropic lateral sclerosis, and schizophrenia, the recent cloning and membrane reconstitution of specific receptors known as AMPA, NMDA, kainate, and metabotropic receptors and their known subunits have prompted a surge of renewed interest in this important family of synaptic transmitter molecules. Moreover, recent advances in our understanding of the molecular events involved in growth promotion in the early stages of the development of the cortex have shown that both NMDA and non-NMDA receptor subtypes perform important roles in certain aspects of target selection and neurite outgrowth, in cone stimulation and guidance, and in spine formation and morphological alterations. A recent explosive growth in interest in the possible roles of nitric oxide and related short-lived radicals in plasticity, disease, and synaptic transmission also is related closely with the actions of excitatory amino acids. All these relatively new advances have transpired in parallel with ongoing work that has extended our appreciation for the roles of excitatory amino acids in the areas of synaptic plasticity (long-term potentiation, long-term depression, receptive field reorganisation following drug-induced or peripheral sensory disturbances, such as denervation or amputation), in processes of normal transmission at functionally and electrophysiologically identified neurones of the cerebral cortex, and in distinct proposed roles for cortical glia. A greater appreciation of the diverse types and properties of the burgeoning family of receptors for the metabotropic receptor also contributed to our desire to feature that aspect of the field in the context of glia and neurones of the cerebral cortex. That part of the field of neuroscience concerned with the functions of excitatory amino acids has grown so large over the past 10 years or so, that a review paper focusing on the contributions to a specialized meeting devoted solely to cerebral cortex could easily be supported by material comprising a sufficient body of communications from top-quality research laboratories. The present account endeavours to summarize and discuss the biochemical characteristics, physiological roles, pharmacological properties, clinical relevance, developmental involvements, and anatomical-morphological aspects pertaining to the excitatory amino acid transmitters in cerebral cortex.
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PMID:Amino acids as the source of considerable excitation in cerebral cortex. 882 81

The neostriatum is the entryway into the basal ganglia and is the site of many of the neurological defects involving basal ganglia function. Thus, it is important to understand the regulation of synaptic transmission at afferent synapses innervating the neostriatum. Cortical glutamatergic and nigral dopaminergic afferent input impinge on neurons in the neostriatum, providing the most significant afferent inputs to this structure. Our understanding of the mechanisms involved in transmission and modulation of transmission at these synapses has greatly increased. It is now apparent that the corticostriatal glutamatergic inputs produce rapid depolarization of striatal neurons via activation of ionotropic AMPA-type glutamate receptors. In addition, transmission is modulated by a number of presynaptic, G-protein-coupled receptors but, surprisingly, relatively little evidence of postsynaptic modulation has been observed. Corticostriatal synapses also express certain forms of plasticity, most notably short- and long- term synaptic depression (STI) and LTD, respectively). It appears that LTD may involve convergent actions of glutamate and dopamine. Striatal LTD may have important roles in information storage and motor set selection in the striatum. However, some aspects of synaptic transmission in the striatum remain unclear. In particular, the exact physiological roles of dopaminergic nigrostriatal input and the role of NMDA-type glutamate receptors are not well understood. In addition, intrastriatal synaptic connections have received relatively little attention as compared with extrinsic input to the neostriatum. Future studies will need to focus on elucidating these aspects of neostriatal function.
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PMID:Synaptic transmission and modulation in the neostriatum. 889 45

1. The effects of histamine on excitatory synaptic transmission in the dentate gyrus region of rat hippocampal slices were examined using extracellular and whole-cell patch-clamp recording techniques. The GABAA receptor antagonist picrotoxin (50 microM) was present in the bath in all experiments. 2. Histamine (0.7-70 microM) reversibly depressed field excitatory postsynaptic potentials (fEPSPs) or excitatory postsynaptic currents (EPSCs) recorded intracellularly by up to 30%. The presynaptic fibre volley and EPSC reversal potential were unaffected by histamine, as were responses following pressure ejection of the glutamate receptor agonist S-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (S-AMPA) into the slice. 3. Histamine (7 microM) depressed equally the AMPA and N-methyl-D-aspartate (NMDA) components of the dual-component EPSC, recorded at -40 mV. 4. In addition to depressing synaptic transmission, histamine also reduced the magnitude of paired-pulse depression (PPD; 40 ms interpulse interval) of the medial perforant path EPSC. 5. Histamine depressed medial perforant path EPSCs more strongly than lateral perforant path EPSCs. Paired-pulse facilitation (PPF; 40 ms interpulse interval) in the lateral perforant path was enhanced by histamine. 6. The effects of histamine on synaptic transmission and PPD were mimicked by the selective H3 receptor agonist R-alpha-methylhistamine (0.1-10 microM) but not by the selective H2 receptor agonist dimaprit (10 microM). Similarly, the H3 receptor antagonist thioperamide (10 microM) blocked the effect of histamine whereas the H1 antagonist mepyramine (1 microM) and the H2 receptor antagonist cimetidine (50 microM) were ineffective. 7. Histamine actions on synaptic transmission and PPD were not occluded by application of the metabotropic glutamate agonist L-2-amino-4-phosphonobutyrate (AP4). 8. The results indicate that histamine depresses synaptic transmission in the dentate gyrus by binding to histamine H3 receptors located on perforant path terminals. The mechanism by which histamine depresses transmission is independent of that used by class III metabotropic glutamate receptors.
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PMID:Histamine H3 receptor-mediated depression of synaptic transmission in the dentate gyrus of the rat in vitro. 891 Feb 6

1. Activity-dependent plasticity of GABAergic synaptic transmission was investigated in neonatal rat hippocampal slices obtained between postnatal day (P) 2-10 using intracellular recording techniques. In all experiments, AMPA receptors were blocked by continual application of CNQX (10 microM). 2. Between P2 and P4, tetanic stimulation (TS) evoked NMDA receptor-dependent long-term depression of monosynaptic GABAA EPSPS (LTDGABAA). In contrast, when NMDA receptors were blocked by D-AP5 (50 microM), the same TS evoke long-term potentiation of GABAA EPSPS (LTPGABAA). 3. Between P6 and P10, TS failed to produce either LTP or LTD or hyperpolarizing monosynaptic GABAA IPSPS under the same recording conditions. However, when GABAergic potentials were rendered depolarizing (KCl-filled electrode) Ts induced either LTPGABAA or LTDGABAA in the presence or absence of D-AP5, respectively. 4. Both LTPGABAA and LTDGABAA were specific to the conditioned pathway and could be sequentially expressed at the same synapses. Potentiation of GABAergic synaptic efficacy was induced more easily following previous induction of LTDGABAA than in naive slices. 5. In conclusion, early in development, bidirectional synaptic plasticity is expressed by GABAA receptors and the activation (or not) of NMDA receptors determines the induction of either LTPGABAA or LTDGABAA.
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PMID:Bidirectional plasticity expressed by GABAergic synapses in the neonatal rat hippocampus. 891 Feb 30

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