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)

1. The postnatal maturation of gamma-aminobutyric acid (GABA)B receptor-mediated presynaptic inhibition was studied in brain slices of rat somatosensory cortex maintained in vitro. Patchclamp techniques were used to record whole-cell inhibitory post-synaptic currents from layer II-III neurons in animals from postnatal days (P) 7-24. Monosynaptic inhibitory postsynaptic currents (IPSCs) were evoked after N-methyl-D-aspartate (NMDA) and non-NMDA type glutamate receptors had been blocked by D-amino-phosphonovaleric acid (D-AP5, 20 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM), respectively. These IPSCs were solely mediated by postsynaptic GABAA receptors because they were abolished by bicuculline (10 microM), reversed polarity near the chloride equilibrium potential, and were recorded with electrodes that contained Cs+ to block postsynaptic GABAB responses. 2. When pairs of stimuli separated by intervals of 0.1-10 s were used to evoke IPSCs, the second response was depressed, an effect that was maximal at 300 ms. Evoked IPSCs were also depressed by baclofen (10 microM). The paired pulse depression (PPD) of monosynaptic IPSCs was decreased or eliminated by 2-OH-saclofen (200 microM). These findings indicate that PPD of monosynaptic IPSCs was due to presynaptic GABAB receptor-mediated inhibition of GABA release. 3. There were no significant differences in the amounts of PPD in neurons from different age groups (P7-10, P12-17, P22-24) at any interstimulus interval tested (0.1-10 s).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential ontogenesis of presynaptic and postsynaptic GABAB inhibition in rat somatosensory cortex. 839 87

GYKI 52466, a non-competitive AMPA/kainate glutamate receptor antagonist, administered in graded doses (0.5-8 mg/kg, i.v.) at 10 min intervals, decreased the amplitude and duration of reflex bladder contractions (maximal inhibition = 63%), the intercontraction interval (maximal inhibition = 83%) and external urethral sphincter activity (maximal inhibition = 91%) in urethane-anesthetized (1.2 g/kg, s.c.) intact rats during continuous transurethral cystometrograms. On the other hand, in unanesthetized decerebrate rats, the drug did not alter reflex bladder activity but did produce a significant depression of sphincter activity (maximal inhibition = 59%). The depressant effects of single doses of GYKI 52466 (4 mg/kg, i.v.) on external urethral sphincter EMG activity occurred with similar time courses in both urethane-anesthetized (1.2 g/kg, s.c.) intact and unanesthetized decerebrate rats during continuous transurethral cystometrograms. In urethane-treated (0.6 g/kg, i.p.) decerebrate rats, GYKI 52466 (0.5-4 mg/kg, i.v.) depressed bladder contraction amplitude and sphincter EMG activity, similar to the effects in urethane-anesthetized (1.2 g/kg, s.c.) intact rats. CNQX (0.01-1 mg/kg, i.v.), a competitive AMPA/kainate receptor antagonist, administered to urethane-anesthetized (1.2 g/kg, s.c.) intact or unanesthetized decerebrate rats did not alter the bladder or the external urethral sphincter activity during continuous transurethral cystometrograms, possibly due to the inability of the drug to readily cross the blood-brain barrier. The present results indicate that glutamatergic excitatory transmission mediated by AMPA/kainate receptors is essential for the activation of external urethral sphincter activity during micturition in anesthetized and unanesthetized preparation. However, the depressant effect of GYKI 52466 on reflex bladder activity is only unmasked by urethane anesthesia, raising the possibility that urethane interacts with AMPA/kainate glutamate receptors in the spinobulbospinal micturition reflex pathway.
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PMID:Effects of GYKI 52466 and CNQX, AMPA/kainate receptor antagonists, on the micturition reflex in the rat. 859 52

1. Whole cell patch-clamp recordings were employed to characterize monosynaptic inhibitory postsynaptic currents (IPSCs) in morphologically and electrophysiologically identified interneurons located in the stratum lacunosum moleculare, or near the border of the stratum radiatum (LM interneurons), in the CA1 region of hippocampal slices taken from 3- to 4-wk-old rats. Monosynaptic IPSCs, evoked in the presence of glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM) and D-2-amino-5-phosphopentanoate (APV; 50 microM) were biphasic. The gamma-aminobutyric acid-A (GABAA) receptor antagonist, bicuculline (20 microM), blocked the fast IPSC, and the slow IPSC was blocked by the GABAB receptor antagonist CGP35348 (500 microM). 2. Monosynaptic IPSCs were evoked by electrical stimulation in several distant regions including the stratum radiatum, the stratum oriens, the stratum lacunosum-moleculare, and the molecular layer of dentate gyrus, suggesting an extensive network of inhibitory interneurons in the hippocampus. In paired recordings of CA1 interneurons and pyramidal cells, IPSCs were evoked by electrical stimulation of most of these distal regions with the exception of the molecular layer of dentate gyrus, which evoked an IPSC only in LM interneurons. 3. Frequent (> 0.1 Hz) stimulation depressed the evoked IPSCs. With a paired-pulse protocol, the second IPSC was depressed and the maximal depression (40-50%) was observed with an interstimulus interval of 100-200 ms. 4. The GABAB receptor agonist baclofen (1 microM) reduced the amplitude of evoked IPSCs and the paired-pulse depression of the second IPSC. The GABAB receptor antagonist CGP35348 (0.5-1 mM) had no significant effect on the amplitude of isolated IPSCs. However, CGP35348 reduced but did not fully block paired-pulse depression, suggesting that this depression is partly due to the activation of presynaptic GABAB receptors. 5. The paired-pulse depression depended on the level of transmitter release. Potentiation of synaptic release of GABA, by increasing the extracellular Ca2+ concentration to 4 mM and reducing the extracellular Mg2+ concentration to 0.1 mM, enhanced the depression. Reduction of transmitter release by increasing extracellular Mg2+ concentration to 7 mM diminished the paired-pulse depression of IPSCs. After potentiation of transmitter release, CGP35348 was less efficient in reducing the paired-pulse depression, suggesting that enhancement of depression by high-calcium/low-magnesium medium was preferentially due to the potentiation of a GABAB-independent component. 6. In summary, monosynaptic IPSCs recorded in LM interneurons show similar features to those recorded in pyramidal cells. The strong correlation between the level of transmitter release and the degree of paired-pulse depression may have important physiological consequences, because in synapses with a high level of activity and a high level of GABA release, inhibition is powerful, but depression can develop more readily.
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PMID:Hippocampal CA1 lacunosum-moleculare interneurons: modulation of monosynaptic GABAergic IPSCs by presynaptic GABAB receptors. 859 1

1. The effects of anoxia on excitatory and inhibitory postsynaptic currents (EPSCs and IPSCs, respectively) evoked by electrical stimulation in the stratum radiatum were studied in morphologically and electrophysiologicaly identified lacunosum-moleculare (LM) interneurons of the CA1 region of rat hippocampal slices. The blind whole cell patch-clamp technique was used, and anoxia was induced by superfusion of the slice with an anoxic artificial cerebral spinal fluid saturated with 95% N2-5% CO2 for 4-6 min. 2. In LM interneurons, anoxia generated currents similar to those in pyramidal cells, the most prominent being anoxic and postanoxic outward currents. The adenosine A1 type receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 200 nM) did not significantly affect anoxia-generated currents. 3. EPSCs and polysynaptic IPSCs (pIPSCs) evoked in LM interneurons by "distant" stimulation (> 1 mm) in the stratum radiatum were strongly depressed by anoxia and recovered upon reoxygenation. 4. Responses to pressure application of glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and N-methyl-D-aspartate (NMDA) were not significantly affected by anoxia, suggesting that the suppression of EPSCs is due to presynaptic mechanisms. 5. DPCPX (200 nM) prevented anoxia-induced suppression of EPSCs, suggesting that this suppression was mediated by presynaptic A1 adenosine receptors. 6. Monosynaptic IPSCs evoked by "close" stimulation (< 0.5 mm) in the stratum radiatum, in the presence of glutamate-receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM) and D-2-amino-5-phosphopentanoate (APV; 50 microM), were reversibly depressed but not blocked by anoxia. 7. Anoxia depressed monosynaptic GABAA receptor-mediated IPSCs (monosynaptic IPSCAs) by inducing a positive shift in the reversal potential and a decrease in slope conductance. Responses to pressure-applied isoguvacine, a GABAA receptor agonist, were reversibly depressed by anoxia, again because of a positive shift in reversal potential and decrease in conductance. Anoxic effects on slope conductances and reversal potential of isoguvacine responses and monosynaptic IPSCA coincided, suggesting that evoked transmitter release from GABAergic terminals was not affected by anoxia. 8. Anoxic depression of monosynaptic GABAB receptor-mediated IPSCs (monosynaptic IPSCBs) was due to a decrease in the slope conductance of monosynaptic IPSCB. In contrast to EPSCs, DPCPX (200 nM) failed to prevent anoxia-induced depression of mIPSCA and mIPSCB. 9. Paired-pulse depression of monosynaptic IPSCs, partially mediated by presynaptic GABAB receptors, was not affected by anoxia. 10. These data provide direct evidence for the hypothesis that inhibitory interneurons of CA1 stratum LM are functionally disconnected from excitatory inputs by anoxia. This disconnection underlies the preferential block by anoxia of IPSCs recorded in pyramidal cells, and it may occult the postsynaptic modifications in GABAA and GABAB responses. This disconnection involves adenosine-dependent inhibition of glutamate release from excitatory terminals. GABA release and its modulation by presynaptic GABAB receptors, both known to be insensitive to adenosine, seems to be resistant to anoxia.
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PMID:Hippocampal CA1 lacunosum-moleculare interneurons: comparison of effects of anoxia on excitatory and inhibitory postsynaptic currents. 859 2

Excitatory postsynaptic currents (EPSCs) were induced in layer II-V pyramidal cells in the frontal cortex of the young rat (postnatal day 14-21) by stimulation of layers II/III in the presence of bicuculline using the whole-cell patch-clamp technique. EPSCs usually consisted of fast and slow components that were sensitive to CNQX and APV, respectively. In response to paired stimuli of identical strength, paired pulse depression (PPD) was seen for these EPSCs. The PPD of fast EPSCs was most pronounced at an interstimulus interval (ISI) of 200-300 msec and ceased to occur at ISIs greater than 3-5 sec, while the PPD of slow EPSCs became most pronounced at an ISI of 500-1000 msec and ceased to occur at ISIs greater than 10 sec. The PPD of fast EPSCs was attenuated by (-)-baclofen (1-5 microM) and removed by 2-hydroxy-saclofen (0.2-0.4 mM). By contrast, the PPD of slow EPSCs consisted of early and late components that were attenuated by (-)-baclofen and muscarine (1-5 microM), respectively. The late PPD of slow EPSCs induced in the presence of baclofen was removed by pirenzepine (1-3 microM). Thus, fast and slow components of glutamatergic EPSCs displayed two distinct PPDs. These results suggest that a part of the glutamatergic afferents likely arising from layer II/III pyramidal cells may terminate predominantly on NMDA receptors in pyramidal cells of the frontal cortex and receive distinct presynaptic inhibition through at least the muscarinic receptors.
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PMID:Differential paired pulse depression of non-NMDA and NMDA currents in pyramidal cells of the rat frontal cortex. 861 60

Confocal laser scanning microscopy was used to study changes in intracellular free calcium concentration ([Ca2+]i) at the level of the soma of cultured hippocampal neurones following pressure application of glutamate or N-methyl-D-aspartate (NMDA). [Ca2+]i was imaged in the presence of tetrodotoxin after loading cells with the fluorescent dye indicator fluo-3/AM. Responses to glutamate were potently antagonized by 6-cyano-7 nitroquinoxaline-2,3-dione (CNQX: 20 microM). They were also strongly and reversibly depressed by 3-((+/-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic acid (CPP; 20 microM), leaving a small CNQX-sensitive component. Responses to NMDA were also blocked by CNQX. In the presence of saturating concentrations of glycine (100 microM), the depression of glutamate or NMDA responses by CNQX was greatly reduced. Exogenously applied glycine also potentiated the NMDA response. These data indicate that the glycine binding site of the NMDA receptor channel is not saturated in cultured hippocampal neurones and thus is susceptible to the action of agonists or antagonists.
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PMID:Changes in intracellular calcium induced by NMDA in cultured rat hippocampal neurons require exogenous glycine. 876 83

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

1. Intracellular recording was used to study the influence of GABAB autoreceptor-mediated regulation of monosynaptic GABAA and GABAB receptor-mediated hyperpolarizing inhibitory postsynaptic potentials (IPSPAs and IPSPBs, respectively) on alpha-amino-3-hydroxy-5-methyl -4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potentials (EPSPAs and EPSPNs, respectively) in the CA1 region of rat hippocampal slices. To achieve this, synaptic potential were evoked monosynaptically by near stimulation following blockade of either EPSPNs, by the NMDA receptor antagonist (R)-2-amino-5-phosphonopentanoate (AP5; 0.05 mM), or EPSPAs, by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 0.01 mM). 2. Paired-pulse stimulation at 3-50 Hz caused an increase in the duration (paired-pulse widening) of EPSPAs, which paralleled the time course of paired-pulse depression of monosynaptic IPSCs, and a potentiation of the amplitude (paired-pulse potentiation) of EPSPAs, which did not. Paired-pulse stimulation also caused frequency-dependent changes in EPSPNs. At frequencies > 40 Hz it produced paired-pulse depression of EPSPNs, along with marked summation of IPSPS, and at frequencies < 40 Hz it caused paired-pulsed enlargement of EPSPNs, concomitant with a reduction in IPSPS. 3. Paired-pulse potentiation of EPSPAs at 50 Hz was enhanced by picrotoxin (0.1 mM) but was not significantly affected by 3-amino-propyl(diethoxymethyl)phosphinic acid (CGP 35348; 1 mM). Paired-pulse depression of EPSPNs at 50 Hz was converted to paired-pulse enlargement by picrotoxin but was unaffected by CGP 35348. These effects can be explained by block of IPSPAs by picrotoxin. 4. Paired-pulsed widening of EPSPAs at 5 Hz was occluded by picrotoxin and abolished by CGP 35348. Similarly, paired-pulsed enlargement of EPSPNs at 5 Hz was occluded, and in some cases converted to paired-pulse depression, by picrotoxin. The effects of CGP 35348 were more complex in that this antagonist reduced paired-pulse enlargement of EPSPNs in control medium whereas it eliminated paired-pulsed depression of EPSPNs in the presence of picrotoxin, effects consistent with its block of GABAB autoreceptors and IPSPBS, respectively. 5. 'Priming' using a 'priming stimulation protocol' (a single 'priming stimulus' followed at 1-50 Hz ('priming frequency') by a 'primed burst' of four shocks at 20-100 Hz ('burst frequency')) caused an increase in both 'primed' EPSPAs and EPSPNs compared with 'unprimed' EPSPAs and EPSPNs. This effect was optimal when the respective priming and burst frequencies were 5 and 100 Hz. 6. In the presence of either picrotoxin or CGP 35348 the primed EPSPAs and EPSPNs resembled unprimed EPSPAs and EPSPNs, respectively. This was because picrotoxin occluded whereas CGP 35348 blocked the effect of priming on EPSPS. 7. CGP 35348 had only modest effects on EPSPAs but enhanced EPSPNs evoked by a tetanus (20 stimuli at 100 Hz), in either the presence or absence of picrotoxin. In the absence of picrotoxin, CGP 35348 also promoted depolarization by enhancing a depolarizing GABAA receptor-mediated component (IPSPD). These effects can all be attributed to block of IPSPBS by CGP 35348. 8. CGP 35348 blocked the induction of long-term potentiation (LTP) of extracellularly recorded field EPSPs elicited by a priming stimulation protocol in control medium but was ineffective in the presence of picrotoxin. CGP 35348 was also ineffective at preventing tetanus-induced LTP (100 Hz, 1 s) in both the absence and presence of picrotoxin. 9. These data demonstrate the complex regulation of AMPA and NMDA receptor-mediated EPSPs during various patterns of synaptic activation caused by the dynamic changes in GABA-mediated synaptic inhibition, which are orchestrated by GABAA autoreceptors in a frequency-dependent
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PMID:Regulation of EPSPs by the synaptic activation of GABAB autoreceptors in rat hippocampus. 891 Feb 29

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

gamma-Aminobutyric acid-B(GABAB) receptor-dependent and -independent components of paired-pulse depression (PPD) were investigated in the rat CA3 hippocampal region. Intracellular and whole cell recordings of CA3 pyramidal neurons were performed on hippocampal slices obtained from neonatal (5-7 day old) and adult (27-34 day old) rats. Electrical stimulation in the hilus evoked monosynaptic GABAA postsynaptic currents (eIPSCs) isolated in the presence of the ionotropic glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and D(-)2-amino-5-phosphovaleric acid (-AP5, 50 microM) with 2(triethylamino)-N-(2,6-dimethylphenyl) acetamine (QX314) filled electrodes. In adult CA3 pyramidal neurons, when a pair of identical stimuli was applied at interstimulus intervals (ISIs) ranging from 50 to 1,500 ms the amplitude of the second eIPSC was depressed when compared with the first eIPSC. This paired-pulse depression (PPD) was partially blocked by P-3-aminoprophyl -P-diethoxymethylphosphoric acid (CGP35348, 0.5 mM), a selective GABAB receptor antagonist. In neonates, PPD was restricted to ISIs shorter than 200 ms and was not affected by CGP35348. The GABAB receptor agonist baclofen reduced the amplitude of eIPSCs in a dose-dependent manner with the same efficiency in both adults and neonates. Increasing the probability of transmitter release with high Ca2+ (4 mM)/low Mg2+ (0.3 mM) external solution revealed PPD in neonatal CA3 pyramidal neurons that was 1) partially prevented by CGP35348, 2) independent of the membrane holding potential of the recorded cell, and 3) not resulting from a change in the reversal potential of GABAA eIPSCs. In adults the GABA uptake blocker tiagabine (20 microM) increased the duration of eIPSCs and the magnitude of GABAB receptor-dependent PPD. In neonates, tiagabine also increased duration of eIPSCs but to a lesser extent than in adult and did not reveal a GABAB receptor-dependent PPD. These results demonstrate that although GABAB receptor-dependent and -independent mechanisms of presynaptic inhibition are present onGABAergic terminals and functional, they do not operate at the level of monosynaptic GABAergic synaptic transmission at early stages of development. Absence of presynaptic autoinhibition of GABA release seems to be due to the small amount of transmitter that can access presynaptic regulatory sites.
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PMID:Ontogenesis of presynaptic GABAB receptor-mediated inhibition in the CA3 region of the rat hippocampus. 949 15

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