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

Activity-dependent competition between two spinal neurons coinnervating an embryonic myocyte was studied in Xenopus cell culture. We have characterized in detail the phenomenon of heterosynaptic suppression by which tetanic stimulation of one neuron results in functional suppression of the synapse made by the untetanized neuron (Lo and Poo, 1991). Fluorescence labeling of the neurons using two different fluorophores revealed that the coinnervating nerve terminals on the spherical myocyte were in close proximity. Heterosynaptic suppression could be induced when the postsynaptic cell was held under either current-clamp or voltage-clamp conditions during the tetanic stimulation. This finding, together with the observation that repetitive postsynaptic depolarization of the myocyte by direct current injection was much less effective in inducing synaptic depression, suggests that postsynaptic ACh receptor activation plays a dominant role in the induction of heterosynaptic suppression. The heterosynaptic suppression appears to be mediated by a rise of Ca2+ levels in the postsynaptic cell, since it was not observed when the cytosolic Ca2+ concentration of the myocyte was buffered at a low level with intracellular loading of a Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA). The dependence of heterosynaptic suppression on the pattern of tetanic stimulation was also studied. At a stimulation frequency of 2 Hz, detectable heterosynaptic suppression could be induced after 20 repetitive stimuli were applied to one of the presynaptic neurons and the suppression was more effective with increasing number of stimuli. Over the range of 0.5-5 Hz, the extent of suppression was independent of the frequency of tetanic stimulation and, in some cells, detectable suppression could be induced at a frequency as low as 0.05 Hz. Except for a few cases, heterosynaptic suppression was found to last for as long as the recording was made after tetanus (up to 1 hr). The fact that the mean amplitude of spontaneous synaptic currents remained the same before and after the suppression while the evoked synaptic currents exhibited higher fluctuation after suppression suggests that the observed synaptic suppression involves a reduction of evoked ACh release from the nerve terminal, although postsynaptic changes have not been excluded. Finally we found that spontaneous synaptic activity may also contribute in part to the synaptic competition between coinnervating nerve terminals. Taken together, these findings provide a quantitative basis for further understanding of activity-dependent competition between developing neuromuscular synapses.
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PMID:Heterosynaptic suppression of developing neuromuscular synapses in culture. 804 43

Effect of postsynaptic activity on the synaptic efficacy was studied in Xenopus nerve-muscle cultures. Repetitive postsynaptic depolarizations induced by injection of current pulses into singly innervated myocytes resulted in significant reduction in the frequency of spontaneous synaptic currents and the amplitude of nerve-evoked synaptic currents at the majority of synapses that showed immature synaptic properties. Repetitive hyperpolarizations and steady depolarizations of similar duration were without effect. The depolarization-induced synaptic depression appeared to result predominantly from a reduced ACh secretion from the presynaptic nerve terminal. Buffering the myocyte cytosolic Ca2+ at a low level with intracellular loading of a Ca2+ buffer, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA), significantly reduced the effect of the depolarizations. Thus postsynaptic electrical activity can regulate the synaptic efficacy of the developing neuromuscular synapases and the regulation may be mediated by retrograde transsynaptic interactions.
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PMID:Depression of developing neuromuscular synapses induced by repetitive postsynaptic depolarizations. 804 44

The effects of chronic ethanol treatment (CET) on cholinergic modulation of CA1 evoked field potentials and recurrent inhibition were investigated in rat hippocampal slices. Densities of muscarinic receptor subtypes were quantified in remaining hippocampal tissue by immunoprecipitation. Iontophoretic application of ACh in stratum pyramidale results in facilitation of single evoked population spikes; application in stratum radiatum results in depression of field EPSPs. CET decreased cholinergic facilitation of population spikes, while cholinergic inhibition of field EPSPs remained unaffected. Integrity of feedback (recurrent) inhibitory circuitry was evaluated by paired-pulse stimulation. As previously demonstrated, recurrent inhibition was significantly reduced after CET; cholinergic disinhibition was also significantly reduced. Thus, CET appears to disrupt a subset of cholinergic effector systems within hippocampal neurons. The reductions in cholinergic function produced by CET does not appear to be due to receptor loss, since muscarinic receptor subtype densities were not found to be significantly altered in this tissue. These results support the hypothesis that muscarinic receptor function is impaired in CA1 pyramidal cells through a disruption of intracellular signal transduction mechanisms. While it is unclear whether cholinergic function is reduced in interneurons directly, these results suggest that modulation of neuronal firing in the hippocampus is markedly altered following CET due to impairment of both cholinergic and GABAergic systems.
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PMID:Effects of chronic ethanol on cholinergic actions in rat hippocampus: electrophysiological studies and quantification of m1-m5 muscarinic receptor subtypes. 813 Oct 51

The purpose of this study was to compare vascular responsiveness in young (12 week old), aging hyperinsulinemic-glucose intolerant (52 weeks old) and diabetic (streptozotocin; 14 weeks old) rats. Aortic rings with and without endothelium were maintained in organ chambers for isometric tension recording. The contractile response to KCl was significantly enhanced in aortae from diabetic animals when compared to the responses obtained in young and old ones. The contractile response to norepinephrine or U46619, was significantly shifted to the right in the aortae from aging animals, however the aortae from these hyperinsulinemic rats were hyperresponsive to serotonin. Acetylcholine and ADP provoked an endothelium-dependent relaxation which was markedly depressed in the aortae from diabetic animals. The relaxation to ADP was selectively inhibited in the aging animals. The effect of sodium-nitroprusside was not significantly different in the three groups. Isoproterenol and forskolin induced endothelium-independent relaxation. Isoproterenol responses were inhibited in aging and diabetic animals, however the forskolin-relaxation was inhibited only in the aortae from aging animals. These results suggest that in two models of diabetes (i.e. Type I insulin-dependent and type II non insulin-dependent) vascular responsiveness is differently affected. Aging hyperinsulinemic animals present a selective hyperresponsiveness to serotonin, a selective dysfunction of ADP-induced endothelium-dependent relaxation and smooth muscle adenylate cyclase deficit. In diabetic animals a beta adrenergic hyporesponsiveness, not linked to adenylate-cyclase dysfunction, and non-selective depression of endothelium-dependent responses can be observed.
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PMID:Vascular responsiveness in young, diabetic, and aging hyperinsulinemic rats. 819 94

Heterosynaptic short-term depression (STD) of the stratum radiatum and stratum oriens inputs to the CA1 region was studied in rat hippocampal slices. STD was evoked by trains of 1050 impulses with interstimulus interval (ISI) variable from 10 to 700 ms. The STD was found to be very pronounced for tetanizations with ISI around 200 ms, and almost absent for ISI less than 50 ms or more than 500 ms. These data show that theta-like tetanization is an effective pattern not only for induction of the long-term potentiation (LTP), as has been shown previously, but for production of the heterosynaptic STD as well. This implies that heterosynaptic STD can effectively modulate induction of LTP by theta-like tetanization, and plays an important role in differentiation of potentiated pathways. It is discussed that the theta-like tetanization-induced release of ACh is a possible mechanism of the STD.
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PMID:Heterosynaptic short-term depression of population spike amplitude in the pyramidal layer of the CA1 hippocampal region evoked by a theta-like tetanization. 833 23

We have investigated the role of the projection from the magnocellular basal forebrain to the olfactory bulb in regulating synaptic transmission in the commissural connection between the two olfactory bulbs. Commissural fibers arise in the contralateral anterior olfactory nucleus, travel in the anterior wing of the anterior commissure (AC), and terminate in the granule cell layer of the olfactory bulb. Electrical stimulation of the commissure causes synaptic activation of granule cells in the granule cell layer of the bulb; the resulting field potential is a reliable indicator of this synaptic current. Microinjections of cholinergic agonists, but not of identical, or larger, quantities of vehicle, reduced the amplitude of this AC field potential. Systemic injection of scopolamine reversed this depression and returned the AC response amplitude to control levels. Irreversible AChE inhibition also reduced the amplitude of the AC response, and muscarinic blockade reversed this effect. Cholinergic terminals in the olfactory bulb arise entirely from the axons of magnocellular basal forebrain neurons in the nucleus of the diagonal band (NDB). Electrical stimulation of NDB, which should release ACh, as well as other transmitters, depressed the AC response. Brief trains of NDB shocks caused a moderate decrease in the AC response that lasted 1-2 sec. Longer shock trains, which caused marked potentiation of the NDB field potential, caused a profound, prolonged (> 20 sec) inhibition of the AC response. Antidromic tests demonstrated that NDB stimulation significantly decreased the excitability of AC terminals. This and other characteristics of the inhibition strongly suggest that the decrease in amplitude of the field potential response to AC stimulation caused by cholinergic agonists and stimulation of NDB is due to presynaptic inhibition leading to reduced release of transmitter from AC terminals. These results suggest that one function of the basal forebrain projection to the olfactory bulb is inhibition of the commissural connection between the two olfactory bulbs. As NDB has been implicated in theta pacemaker input to the olfactory bulb, phasic NDB inhibition of centrifugal afferents to the bulb could function to coordinate signal processing temporally in the olfactory system. Temporal coordination may be particularly important to olfactory circuit function, as this system lacks the point-to-point topographical organization characteristic of other sensory systems.
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PMID:Evidence for presynaptic inhibition of the olfactory commissural pathway by cholinergic agonists and stimulation of the nucleus of the diagonal band. 842 31

In rats lesioned by injecting the ibotenic acid (8 micrograms/site) into the unilateral nucleus basalis magnocellularis (NBM), the effect of treatment with bifemelane hydrochloride (BIF) or autotransplantation of the vagal nodosal ganglion was studied electrophysiologically by serial measurement of the event-related potential (ERP, P300) for 4 weeks. In addition, the effects on cholinergic markers were assessed by determining the specific binding of [3H]QNB (quinuclidinyl benzilate) to the muscarinic acetylcholine receptor (mAChR) as well as the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE). The P300 latency was delayed and its amplitude remained low for 4 weeks in NBM-lesioned rats. In contrast, a return to normal occurred after 2-3 weeks in rats given daily intraperitoneal injections of BIF (15 mg/kg) and in autotransplanted rats. In lesioned rats, the cortical ChAT and AChE activities on the affected side did not recover, but the postsynaptic receptor response was transiently activated soon after lesioning. BIF increased specific mAChR binding (an early increase of affinity and a subsequent increase of receptor density) as well as presynaptic ChAT activity. Transplantation achieved the early activation of mAChR binding (increased receptor density) and continuously increased ChAT activity. Thus, the postsynaptic compensatory receptor mechanism of denervation supersensitivity acted as an early response to the depression of presynaptic cholinergic activity, but it could not improve the P300 response until the subsequent increase of cortical ChAT activity. Improvement of P300 combined with cortical cholinergic recovery after nodosal ganglion grafting or administration of BIF suggests that the neocortical ACh level may play an important role in regulating ERP.
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PMID:Effect of vagal autotransplantation and bifemelane hydrochloride on cholinergic markers and event-related potentials in rats with lesions of the nucleus basalis magnocellularis. 854 4

1. Rings of bovine left anterior descending coronary artery (LAD) were contracted with the thromboxane A2-mimetic, U46619 (1-30 nM), to approximately 40% of their maximum contraction to 125 mM KCl Krebs solution (KPSSmax) for comparison of responses to the B1 and B2 kinin receptor agonists, des-Arg9-bradykinin (des-Arg9-BK) and bradykinin (BK), respectively. Relaxation responses were normalized as percentages of the initial U46619-induced contraction level, while contractile responses were expressed as percentages of KPSSmax. 2. After 6 h of in vitro incubation in Krebs solution at 37 degrees C, des-Arg9-BK (pEC50, 8.00 +/- 0.08; maximum response (Rmax), 93.9 +/- 1.9%) and BK (pEC50, 9.75 +/- 0.07; Rmax, 100.1 +/- 0.7%) caused endothelium-dependent relaxations in precontracted rings of bovine LAD which were competitively and selectively antagonized by the B1 receptor antagonist, des-Arg9-[Leu8]-BK (pA2, 6.27 +/- 0.11) and the B2 receptor antagonist Hoc-140 (pA2, 9.63 +/- 0.14), respectively. 3. At 3 h of in vitro incubation, the sensitivity (pEC50, 7.45 +/- 0.10) and Rmax (84.6 +/- 3.3%) to des-Arg9-BK were significantly less than those obtained in the same tissues at 6 h (pEC50, 7.94 +/- 0.06; Rmax, 91.4 +/- 2.5%), whereas endothelium-dependent relaxations to BK and ACh were unaffected by incubation time. 4. Relaxation responses to des-ARg9-BK, but not BK, at both 3 h and 6 h were significantly attenuated by the protein synthesis inhibitors, cycloheximide (30 and 100 microM) and actinomycin D (2 microM). 5. At 6 h, the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (L-NOARG, 100 microM), caused a significant 2 fold decrease in pEC50 (9.58 +/- 0.03) but had no effect on Rmax for BK. For des-Arg9-BK, L-NOARG (100 microM) caused a marked and significant decrease in both the pEC50 and Rmax and revealed contractions to low concentrations of des-Arg9-BK. In both cases, L-NOARG inhibition was reversed in the presence of L-arginine (10 mM). 6. At 6 h removal of the endothelium abolished relaxation responses to des-Arg9-BK and BK, and for des-Arg9-BK, but not BK, unmasked concentration-dependent contractions (pEC50, 7.57 +/- 0.09; Rmax, 83.4 +/- 9.1%). The sensitivity of contractions to des-Arg9-BK increased slightly from 3 h (pEC50, 7.37 +/- 0.08) to 6 h (pEC50, 7.62 +/- 0.12) of in vitro incubation; however, there was a small but significant depression in the maximum response over this time (Rmax, 126.8 +/- 8.5% and 103.3 +/- 8.6% for 3 h and 6 h of incubation respectively). 7. In conclusion, the bovine LAD contains inducible B1 and constitutive B2 endothelial cell kinin receptors, both of which mediate endothelium-dependent relaxation partly via the release of NO. B1 receptors were also present on the smooth muscle layer of the bovine LAD.
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PMID:Endothelium-dependent relaxations mediated by inducible B1 and constitutive B2 kinin receptors in the bovine isolated coronary artery. 858 Dec 87

1. By use of patch-clamp techniques, the effects of SD-3212, a novel antiarrhythmic drug, on the calcium current (Ica), the sodium current (INa) and the muscarinic acetylcholine-receptor-operated potassium current (IK.ACh) were examined and compared with those of bepridil in guinea-pig single atrial cells. 2. SD-3212 inhibited ICa and INa in a concentration-dependent manner. The IC50 values of SD-3212 for inhibition of ICa and INa were 1.29 microM and 3.92 microM, respectively. The steady state inactivation curves of ICa and INa were shifted in the hyperpolarizing direction in the presence of 1 microM SD-3212. Similar inhibition of ICa and INa was also observed with bepridil. The IC50 values of bepridil for depression of ICa and INa were 1.55 microM and 4.43 microM, respectively. 3. The muscarinic acetylcholine-receptor-operated potassium current (IK.ACh) was activated by the extracellular application of 1 microM carbachol in the GTP-loaded cells or by the intracellular loading of GTP gamma S, a nonhydrolysable GTP analogue. SD-3212 potently inhibited the carbachol- and GTP gamma S-induced IK.ACh and the IC50 values were 0.38 microM and 0.20 microM, respectively. These IC50 values were very close and about 10 times lower than those for inhibiting ICa and INa. Bepridil also suppressed the carbachol- and GTP gamma S-induced IK.ACh with the IC50 values of 0.69 microM and 0.84 microM, respectively. 4. In guinea-pig atrial cells stimulated at 0.2 Hz, carbachol at a concentration of 1 microM markedly shortened action potential duration. Both SD-3212 (0.1-1 microM) and bepridil (1-10 microM) reversed the action potential shortening in a concentration-dependent manner. The antagonizing effect of SD-3212 on the carbachol-induced action potential shortening was more potent than that of bepridil. 5. These results suggest that SD-3212 inhibits IK.ACh by depressing the function of the potassium channel itself and/or associated GTP-binding proteins. SD-3212 is a unique antiarrhythmic drug, which potently inhibits IK.Ach in addition to its class I and IV effects. SD-3212 and bepridil may be useful for the termination and prevention of vagally-induced atrial flutter and fibrillation.
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PMID:SD-3212, a new class I and IV antiarrhythmic drug: a potent inhibitor of the muscarinic acetylcholine-receptor-operated potassium current in guinea-pig atrial cells. 859 Oct

Synaptic activity is known to modulate neuronal connectivity in the nervous system. At developing Xenopus neuromuscular synapses in culture, repetitive postsynaptic application of ACh near the synapse leads to immediate and persistent synaptic depression, which was shown to be caused by reduction of presynaptic evoked transmitter release. However, little depression was found when ACh was applied to the muscle 20 microns or further from the synapse. Fluorescence imaging of cytosolic Ca2+ ([Ca2+]i) showed that each ACh pulse induced a transient elevation of myocyte [Ca2+]i that spread approximately 20 microns. Local photoactivated release of Ca2+ from the caged Ca2+ chelators nitr-5 or nitrophen in the postsynaptic cell was sufficient to induce persistent synaptic depression. These results support a model in which localized Ca2+ influx into the postsynaptic myocyte initiates transsynaptic retrograde modulation of presynaptic secretion mechanisms.
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PMID:Postsynaptic elevation of calcium induces persistent depression of developing neuromuscular synapses. 860 93


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