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

Excitatory postsynaptic currents (EPSCs) in parasympathetic preganglionic neurons (PGNs) were examined using the whole cell patch-clamp recording technique in L6 and S1 spinal cord slices from neonatal rats (6-16 days old). PGNs were identified by labeling with retrograde axonal transport of a fluorescent dye (Fast Blue) injected into the intraperitoneal space 3-7 days before the experiment. Synaptic responses were evoked in PGNs by field stimulation of the lateral funiculus (LF) in the presence of bicuculline methiodide (10 microM) and strychnine (1 microM). In approximately 40% of the cells (total, 100), single-shock electrical stimulation of the LF elicited short, relatively constant latency [3.0 +/- 0.1 (SE) ms] fast EPSCs consistent with a monosynaptic pathway. The remainder of the cells did not respond to stimulation. At low intensities of stimulation, the EPSCs often occurred in an all-or-none manner, indicating that they were mediated by a single axonal input. Most cells (n = 33) exhibited only fast EPSCs (type 1), but some cells (n = 8) had fast EPSCs with longer, more variable latency polysynaptic EPSCs superimposed on a slow inward current (type 2). Type 1 fast synaptic EPSCs were pharmacologically dissected into two components: a transient component that was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5 microM), a non-NMDA glutamatergic antagonist, and a slow decaying component that was blocked by 2-amino-5-phosphonovalerate (APV, 50 microM), a NMDA antagonist. Type 2 polysynaptic currents were reduced by 5 microM CNQX and completely blocked by combined application of 5 microM CNQX and 50 microM APV. The fast monosynaptic component of type 1 EPSCs had a linear current-voltage relationship and reversed at a membrane potential of 5.0 +/- 5.9 mV (n = 5), whereas the slow component exhibited a negative slope conductance at holding potentials greater than -20 mV. The type 1, fast synaptic EPSCs had a time to peak of 1.4 +/- 0.1 ms and exhibited a biexponential decay (time constants, 5.7 +/- 0.6 and 38.8 +/- 4.0 ms). In the majority of PGNs (n = 11 of 15 cells), EPSCs evoked by electrical stimulation of LF exhibited paired-pulse inhibition (range; 25-33% depression) at interstimulus intervals ranging from 50 to 120 ms. These results indicate that PGNs receive monosynaptic and polysynaptic glutamatergic excitatory inputs from axons in the lateral funiculus.
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PMID:Excitatory synaptic currents in lumbosacral parasympathetic preganglionic neurons elicited from the lateral funiculus. 1160 Jun 22

The effectiveness of tetraethylammonium (TEA) and high-frequency stimulation (HFS) in inducing long-term synaptic modification is compared in CA1 and dentate gyrus (DG) in vitro. High-frequency stimulation induces long-term potentiation (LTP) at synapses of both perforant path-DG granule cell and Schaffer collateral-CA1 pyramidal cell pathways. By contrast, TEA (25 mM) induces long-term depression in DG while inducing LTP in CA1. The mechanisms underlying the differential effect of TEA in CA1 and DG were investigated. It was observed that T-type voltage-dependent calcium channel (VDCC) blocker, Ni2+ (50 microM), partially blocked TEA-induced LTP in CA1. A complete blockade of the TEA-induced LTP occurred when Ni2+ was applied together with the NMDA receptor antagonist, D-APV. The L-type VDCC blocker, nifidipine (20 microM), had no effect on CA1 TEA-induced LTP. In DG of the same slice, TEA actually induced long-term depression (LTD) instead of LTP, an effect that was blocked by D-APV. Neither T-type nor L-type VDCC blockade could prevent this LTD. When the calcium concentration in the perfusion medium was increased, TEA induced a weak LTP in DG that was blocked by Ni2+. During exposure to TEA, the magnitude of field EPSPs was increased in both CA1 and DG, but the increase was substantially greater in CA1. Tetraethylammonium application also was associated with a large, late EPSP component in CA1 that persisted even after severing the connections between CA3 and CA1. All of the TEA effects in CA1, however, were dramatically reduced by Ni2+. The results of this study indicate that TEA indirectly acts via both T-type VDCCs and NMDA receptors in CA1 and, as a consequence, induces LTP. By contrast, TEA indirectly acts via only NMDA receptors in DG and results in LTD. The results raise the possibility of a major synaptic difference in the density and/or distribution of T-type VDCCs and NMDA receptors in CA1 and DG of the rat hippocampus.
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PMID:Differential effect of TEA on long-term synaptic modification in hippocampal CA1 and dentate gyrus in vitro. 1172 43

We investigated the acute effects of bath applied BDNF on synaptic input to motoneurons in the hemisected spinal cord of the neonatal rat. Motoneurons were recorded intracellularly, and BDNF-induced modulation of the synaptic response to stimulation of the homologous dorsal root (DR) and the ventrolateral funiculus (VLF) was examined. All motoneurons exhibited long-lasting (up to several hours) depression of the DR-activated monosynaptic AMPA/kainate-receptor mediated EPSP in response to BDNF but in about half of the motoneurons this was preceded by facilitation. VLF-evoked AMPA/kainate EPSPs in the same motoneurons were unaffected. BDNF effects were blocked by K252a and were not observed in neonates older than 1 week. Bath applied NMDA antagonists APV and MK-801 abolished both facilitatory and inhibitory actions of BDNF on the AMPA/kainate responses indicating the requirement for functional NMDA receptors. The pharmacologically isolated, DR-evoked, NMDA receptor-mediated response exhibited the same pattern of changes after BDNF superfusion. When introduced into the motoneuron through the recording microelectrode, MK-801 selectively blocked the facilitatory action of BDNF. Furthermore, BDNF enhanced NMDA-induced depolarization of the motoneuron in the presence of tetrodotoxin (TTX), thus, confirming its facilitatory effect on motoneuron NMDA receptors. Bath application of either BDNF or NMDA depressed the monosynaptic EPSP after selective blockade of postsynaptic NMDA receptors indicating a role for presynaptic NMDA receptors in BDNF-induced inhibitory action. Thus, BDNF-induced facilitation of monosynaptic EPSPs in neonatal rats is mediated by direct effects on postsynaptic NMDA receptors, while its inhibitory action occurs presynaptically.
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PMID:Acute modulation of synaptic transmission to motoneurons by BDNF in the neonatal rat spinal cord. 1186 Apr 75

The developing retinocollicular pathway undergoes synaptic refinement in order to form the precise retinotopic pattern seen in adults. To study the mechanisms which underlie refinement, we investigated long-term changes in retinocollicular transmission in rats aged P0-P25. Field potentials (FPs) in the superior colliculus (SC) were evoked by stimulation of optic tract fibers in an in vitro isolated brainstem preparation. High intensity stimulation induced long-term depression (LTD) in the SC after both low (1000 stimuli at 1 Hz) and higher (1000 stimuli at 50 Hz) frequency stimulation. The induction of LTD was independent of activation of NMDA and GABA(A) receptors, because D-APV (100 microM) and bicuculline (10 microM) did not block LTD. Induction of LTD was dependent upon activation of L-type Ca(2+) channels as 10 microM nitrendipine, an L-type Ca(2+) channel blocker, significantly decreased the magnitude of LTD. LTD was down-regulated during development. LTD magnitude was greatest in rats aged P0-P9 and significantly less in rats aged P10-P25. Long-term potentiation (LTP) was induced by low intensity stimulation and only after high frequency tetanus (1000 stimuli at 50 Hz). LTP was NMDA receptor dependent because d-APV (100 microM) completely abolished it. LTP induction was also blocked by the L-type Ca2+ channel blocker nitrendipine. The magnitude of LTP first increased with age, being significantly greater at P7-P13 than at P0-3 and then decreased at P23-25. In summary, both LTD and LTP are present during retinocollicular pathway refinement, but have different transmitter and ionic mechanisms and time courses of expression.
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PMID:Properties of LTD and LTP of retinocollicular synaptic transmission in the developing rat superior colliculus. 1202 52

Several lines of evidence indicate a substantial contribution of kainate receptors to temporal lobe seizures. The activation of kainate receptors located on hippocampal inhibitory interneurons was shown to reduce GABA release. A reduced GABA release secondary to kainate receptor activation could contribute to an enhanced seizure susceptibility. As the dentate gyrus serves a pivotal gating function in the spread of limbic seizures, we tested the role of kainate receptors in the regulation of GABA release in the dentate gyrus of control and kindled animals. Application of glutamate (100 micro m) in the presence of the NMDA receptor antagonist d-APV and the AMPA receptor antagonist, SYM 2206 caused a slight depression of evoked monosynaptic inhibitory postsynaptic currents (IPSCs) in control, but a substantial decrease in kindled dentate granule cells. The observation that kainate receptor activation altered paired-pulse depression and reduced the frequency of TTX-insensitive miniature IPSCs without affecting their amplitude is consistent with a presynaptic action on the inhibitory terminal to reduce GABA release. In kindled preparations, neither glutamate (100 micro m) nor kainate (10 micro m) applied in a concentration known to depolarize hippocampal interneurons led to an increase of the TTX-sensitive spontaneous IPSC frequency nor to changes of the postsynaptic membrane properties. Consistently, the inhibitory effect on evoked IPSCs was not affected by the presence of the GABAB receptor antagonist, CGP55845A, thus excluding a depression by an enhanced release of GABA acting on presynaptic GABAB receptors. The enhanced inhibition of GABA release following presynaptic kainate receptor activation favours a use-dependent hyperexcitability in the epileptic dentate gyrus.
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PMID:Kindling enhances kainate receptor-mediated depression of GABAergic inhibition in rat granule cells. 1237 22

The effects of Ptychodiscus brevis toxin (PbTx) on the Ia-alpha motoneuron synaptic transmission in neonatal rat spinal cord in vitro was examined. The stimulation of a dorsal root evoked monosynaptic (MSR) and polysynaptic reflex (PSR) potentials in the segmental ventral root in Mg2+-free medium. Superfusion with PbTx (2.8-84 microM) depressed the MSR and the PSR in a concentration-dependent manner. At 2.8 microM of PbTx, the depression of MSR and PSR was 24+/-8.3% and 37+/-9.7%, respectively. The maximal depression was seen at 84 microM of the toxin (78% for MSR and 96% for PSR). The concentration of toxin required to produce 50% depression was 28.3+/-6.4 microM for MSR and 5.5+/-1.1 microM for PSR. The PbTx (28 microM) did not alter the magnitude of the dorsal root or the ventral root potentials. Addition of MgSO4 (1.3 mM) or DL-2-amino-5-phosphonovaleric acid (APV; 10 microM) to the physiological solution abolished the PSR totally and decreased the MSR by about 30%. In both the conditions, the PbTx-induced depression of the MSR was attenuated significantly. The PbTx-induced depression was blocked completely in the presence of APV+6-cyano-7-nitroquinoxaline-2,3-dione (0.1 microM). NMDA (1 microM) by itself did not alter the magnitude of MSR or PSR but enhanced the PbTx-induced depression (28 microM) of PSR significantly. 7-Chlorokynurenic acid (3 microM; glycine(B) antagonist) did not block the PbTx-induced depression of MSR. D-serine (glycine(B) agonist) did not reverse the PbTx-induced depression of reflexes although it reversed the 7-chlorokynurenic acid-induced depression of PSR. The results indicate that the PbTx depressed the spinal reflexes without altering the magnitude of dorsal root or ventral root activity. The depression of the PSR involved NMDA receptors while that of the MSR involved NMDA and non-NMDA receptors. The PbTx actions did not involve the glycine(B) site of the NMDA receptor.
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PMID:Involvement of N-methyl-D-aspartate receptors for the Ptychodiscus brevis toxin-induced depression of monosynaptic and polysynaptic reflexes in neonatal rat spinal cord in vitro. 1245 90

In our previous studies, we have shown that in vitro biaxial strain (stretch) injury of neurons in neuronal plus glial cultures increases intracellular free calcium ([Ca(2+)](i)) and decreases mitochondrial membrane potential (deltapsi(m)). The goal of this study was to determine whether strain injury, without the addition of exogenous agents, causes glutamate release, and whether NMDA receptor antagonists affect the post-strain injury rise in [Ca(2+)](i) and decrease in deltapsi(m). [Ca(2+)](i) and deltapsi(m) were measured using the fluorescent indicators fura-2 AM and rhodamine-1,2,3 (rh123). Strain injury of neuronal plus glial cultures caused an immediate 100-200 nM elevation in neuronal [Ca(2+)]i and a decline in neuronal deltapsi(m) by 15 min post-injury. Pretreatment with the NMDA receptor antagonist MK-801 (10 microM) attenuated the [Ca(2+)](i) elevation after mild, but not moderate and severe injury. MK-801 pretreatment reduced the decline in deltapsi(m) after mild and moderate, but not after severe injury. The NMDA receptor antagonist D-2-amino-5-phosphonopentanoic acid (APV; 100 microM) had effects similar to MK-801. Simultaneous measurement of [Ca(2+)](i) and deltapsi(m) demonstrated a significant correlation and a temporal relationship between [Ca(2+)](i) elevation and depression of deltapsi(m). We conclude that NMDA receptor stimulation contributes to some of the changes in [Ca(2+)](i) and deltapsi(m) after less severe strain injury. However, after more pronounced injury other mechanisms appear to be more involved.
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PMID:NMDA receptor activation contributes to a portion of the decreased mitochondrial membrane potential and elevated intracellular free calcium in strain-injured neurons. 1254 62

Substance P (SP) is an undecapeptide that is co-localized with conventional transmitters in the nucleus accumbens (NAc). Its neurochemical and behavioral effects resemble those of cocaine and amphetamine. How SP accomplishes these effects is not known, partly because its cellular and synaptic effects are not well characterized. Using whole cell and nystatin-perforated patch recording in rat forebrain slices, we show here that SP, an excitatory neuropeptide, depresses evoked excitatory postsynaptic currents (EPSCs) and potentials (EPSPs) in NAc through intermediate neuromodulators. SP caused a partially reversible, dose-dependent decrease in evoked EPSCs. This effect was mimicked by a neurokinin-1 (NK1) receptor-selective agonist, [Sar(9), Met (O(2))(11)]-SP and blocked by a NK1 receptor-selective antagonist, L 732 138. Both the SP- and [Sar(9), Met (O(2))(11)]-SP-induced synaptic depressions were accompanied by increases in paired pulse ratio (PPR), effects that were also blocked by L 732 138. In contrast to its effect on PPR, SP did not produce significant changes in the holding current, input resistance, EPSC decay rate (tau), and steady-state I-V curves of the recorded cells. The SP-induced synaptic depressions were prevented by dopamine receptor blockade using SCH23390 and haloperidol, but not by sulpiride. In addition, the SP-induced synaptic depression was blocked by an adenosine A1 receptor blocker 8-cyclopentyltheophylline (8-CPT) but not the N-methyl-D-aspartate (NMDA) receptor antagonist D-APV. These data show that SP, by activating presynaptic NK1 receptors, depresses excitatory synaptic transmission indirectly by enhancing extracellular dopamine and adenosine levels. Since the cellular and synaptic effects of SP resemble those of cocaine and amphetamine, it may serve as an endogenous psychogenic peptide.
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PMID:Substance P depresses excitatory synaptic transmission in the nucleus accumbens through dopaminergic and purinergic mechanisms. 1257 50

Thyroid hormone deficiency during a critical period of development profoundly affects cognitive functions such as attention, learning, and memory, but the synaptic alterations underlying these deficits remain unexplored. The present study examines the effect of congenital hypothyroidism on long-term synaptic plasticity. This plasticity is believed to be essential for learning and memory and for activity-dependent regulation of synapse formation in the developing brain. We found that the neonatal expression of long-term potentiation (LTP), long-term depression (LTD), depotentiation, and de-depression in hippocampal slices from hypothyroid animals was similar to that of controls. To examine the postnatal development of these plasticities, we used slices from neonatal (2-3 weeks) and adult (7-8 weeks) rats. This work demonstrates that the ability to express all these forms of synaptic plasticity is reduced in an age-dependent manner in control rats. LTP and depotentiation are also downregulated in adult hypothyroid rats, but we have found that de-depression is not affected during maturation. In addition, these animals express LTD at ages at which controls fail to induce it. In contrast, input/output experiments have shown greater levels of basal synaptic efficacy in hypothyroid adults, and this effect is probably related to the higher probability of release observed by paired-pulse experiments. Nevertheless, these effects appear to be unrelated to the differences observed in long-term synaptic plasticity, as no correlation was found between basal synaptic efficacy and the degree of LTD and de-depression. Furthermore, the NMDA-receptor antagonist amino-phosphonopentanoic acid (APV) completely blocked LTD, which suggests a postsynaptic locus of this alteration. Because LTD has been associated with novelty acquisition, we suggest that the greater LTD observed in adult hypothyroid rats might be related to the hyperactivity of these animals. However, other possibilities such as a retarded maturation of synaptic plasticity must be taken into account.
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PMID:Age-dependent alterations of long-term synaptic plasticity in thyroid-deficient rats. 1462 Aug 77

We have previously reported that dopamine (DA) depresses non-NMDA receptor-mediated glutamatergic transmission in the rat parabrachial nucleus (PBN), an interface between brainstem and forebrain that is implicated in autonomic regulation. This work examined cellular signalling pathways that might underlie this DA-induced synaptic depression. Direct activation of adenylyl cyclase with 10 microM forskolin increased the evoked EPSC but did not occlude DA-induced EPSC depression. Similarly, a preferential protein kinase A inhibitor, H-7 (10 microM), did not block DA's synaptic effects. Incubation of slices with cholera toxin (CTX; 1 microgram/ml) or pertussis toxin (PTX; 0.5 microgram/ml) for 20 h, procedures used to irreversibly activate or disable the G(s) and G(i) proteins, respectively, did not change DA's effects. The putative phospholipase C inhibitor, U-73122 (10 microM) and its inactive analogue U-73343 (10 microM) did not alter DA-induced reduction in the EPSCs. Alterations in signalling molecules downstream of phospholipase C including depleting internal calcium stores by thapsigargin and cyclopiazonic acid and blocking protein kinase C with chelerythrine, had no effect on DA-induced synaptic depression. Furthermore, DA's depression of the non-NMDA response was not blocked by APV, an NMDA receptor antagonist. Finally, DA depressed evoked, pharmacologically isolated NMDA receptor-mediated synaptic responses while increasing NMDA-induced inward currents in the PBN. These results indicate that DA-induced synaptic effects in the PBN are not through the activation of cholera or pertussis toxin sensitive G proteins. Furthermore, it does not employ the adenylyl cyclase-cAMP-PKA cascade, the phospholipase C signalling pathway and NMDA receptor-coupled mechanisms to depress excitatory synaptic transmission in the PBN.
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PMID:Dopamine-induced synaptic depression in the parabrachial nucleus is independent of CTX- and PTX-sensitive G-proteins, PKA and PLC signalling pathways. 1467 13


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