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

An abnormal electrophysiological response in brain slices of the dentate gyrus from biopsy material from patients surgically treated for intractable epilepsy (46/57), exhibited characteristics similar to the physiological hallmark of epilepsy, the paroxysmal discharge, a prolonged (30-600 ms) and often large amplitude field potential. The most striking feature of the prolonged response to a single perforant path stimulus was a predominantly biphasic field potential (23/46 cases). The biphasic response was characterized by a negative field potential of substantial duration exceeding 180 ms which followed an initial shorter duration positive field potential. Multiple population spikes occurred during both phases of the response. During a 1 Hz stimulus train applied to the perforant path, the magnitude and duration of the negative component of the field response was significantly increased. Approximately half of the cases (Group 1; 30/57) exhibited potentiation of the biphasic response, while the remaining cases (Group 2; 27/57) exhibited no negative field component during 1 Hz stimulation trains. This repetitive stimulation, in general, increased the area of the field response in a large majority of cases (44/57) regardless of the sign of the field potential. The number of population spikes following 1 Hz stimulation increased significantly for cases in both groups, although the increase was greater for those in Group 1 than in Group 2. Paired pulse depression (20 ms ISI) was reduced in cases that exhibited potentiated biphasic responses during 1 Hz stimulation (Group 1) in comparison to cases that exhibited no negative field potentials (Group 2). Paired pulse depression at a 200 ms ISI was not significantly different between the groups. During a single stimulus, bicuculline disinhibition (20 microM) resulted in either a prolonged positive or biphasic field potential. Intracellularly recorded responses to single perforant path stimuli also exhibited prolonged and large depolarizations that were comparable in time course to the duration of field potentials recorded in the same area whether generated in the absence or presence of bicuculline. The prolonged field potential after bicuculline was reduced by APV (20 microM). We suggest that the prolonged field response, whether biphasic or monophasic when generated by either 1 Hz stimulation or bicuculline disinhibition, may be due directly or indirectly to an increase in membrane depolarization mediated by activation of the NMDA receptor.
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PMID:Prolonged field potentials evoked by 1 Hz stimulation in the dentate gyrus of temporal lobe epileptic human brain slices. 879 93

The effect of N-methyl-D-aspartate (NMDA) on the function of GABAA receptors was examined in acutely dissociated neurons of bullfrog dorsal root ganglia (DRG) by using whole-cell patch clamp methods. The application of NMDA (100 microM) to DRG neurons suppressed the inward currents produced by GABA (100 microM) and muscimol (100 microM). DL-2-Amino-5-phosphonovaleric acid (APV; 100 microM) antagonized the NMDA-induced depression of the GABA current in a competitive manner. Kainic acid (100 microM) did not depress the GABA current. NMDA induced no depression of the GABA current in a nominally Ca(2+)-free solution containing 5 mM Mg2+. These data indicate that the activation of the NMDA receptor inhibits the GABAA receptor-mediated current via a Ca(2+)-dependent process.
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PMID:N-methyl-D-aspartate depresses GABAA receptor-mediated currents in neurons of bullfrog dorsal root ganglia. 882 52

The effects of tetrahydro-9-aminoacridine (THA) on beta-adrenoceptor activation-induced synaptic potentiation were studied in brain slices of the rat amygdala using intracellular recording techniques. To exclude the involvement of N-methyl-D-aspartate (NMDA) receptors, all the experiments were performed in the presence of NMDA receptor antagonist, D-APV (50 microM). Bath application of isoproterenol (Iso; 15 microM) results in a long-lasting enhancement of the amplitude of excitatory postsynaptic potentials (EPSPs) to 200 +/- 6% of baseline. Forskolin, which directly activates adenyl cyclase, produces a similar effect suggesting that Iso may act through a cyclic AMP-dependent mechanism. Pretreatment of the slices with THA (300 microM) completely abolishes the Iso- and forskolin-induced synaptic potentiation. We hypothesize that the locus of THA/beta-adrenoceptor interaction is presynaptic; the underlying mechanism is likely due to THA's depression of transmitter release via a presynaptic blockade of voltage-dependent Ca2+ channels.
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PMID:Blockade of isoproterenol-induced synaptic potentiation by tetra-9-aminoacridine in the rat amygdala. 887 90

One important question concerning the homeostatic regulation of many physiological processes is whether the control mechanisms are purely reflexogenic or whether they may involve neural adaptation in the form of learning and memory in the brainstem. Using a brainstem slice preparation in the rat, we studied the modifiability of neural transmission in the first-order synapses of the medial and commissural nucleus tractus solitarius of the medulla. Sustained low-frequency stimulation (5 Hz) of primary afferent fibers in the tractus solitarius resulted in a phasic depression (accommodation) of synaptic strength as reflected by a concomitant decrease in the evoked excitatory postsynaptic potentials. In one group of neurons (type I), synaptic strength recovered rapidly after low-frequency stimulation, whereas in another group of neurons (type II), synaptic strength remained depressed for >30 min, i.e., manifesting long-term depression (LTD). The latter was switched into a short-term depression lasting 15-25 min after pharmacological blockade of NMDA receptor channels with D-APV or chelation of intracellular calcium ions with EGTA, whereas the accommodation phase was unaffected. Application of an AMPA receptor anti-desensitization agent cyclothiazide abolished the LTD, but not the accommodation response. These results suggest the presence of separate postsynaptic sites for the induction of LTD and accommodation, one being sensitive to cyclothiazide, whereas the other is not. Moreover, the maintenance of LTD is dependent on the level of intracellular Ca2+. These phasic and long-term synaptic plasticity in the nucleus tractus solitarius may play a role in the homeostatic regulation of cardiorespiratory functions.
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PMID:Phasic and long-term depression in brainstem nucleus tractus solitarius neurons: differing roles of AMPA receptor desensitization. 920 19

The EL/Suz (EL) mouse is a strain that is highly susceptible to convulsive seizures after repeated sensory stimulation. Its control strain, DDY/Jc1 (DDY), is less susceptible under similar conditions. The seizure prone phenotype is the result of differences at several genetic loci. In vivo electrical recordings from the seizure prone EL mouse brain have shown that the appearance of abnormal discharges in the hippocampus are critical to the onset of generalized seizures, indicating that the hippocampus plays an important role in EL mouse seizure activity. In the present study, electrophysiological differences between EL and DDY mice (9-15 weeks of age) were examined by comparing field potentials recorded from the dentate granule cell layer of hippocampal brain slices from mice that had not been stimulated to induce seizures. In control physiological solution, no significant differences were observed in characteristics of perforant path evoked field potentials or in paired pulse depression of evoked field potentials using 20 to 300 ms interstimulus intervals. After 60 min of disinhibition following bicuculline (10 microM) exposure, however, prolonged large amplitude potentials, paroxysmal discharges, were evoked by perforant path stimulation in the dentate gyrus of EL mice but were absent in the DDY strain. Paroxysmal discharges were curtailed by APV and were similar to responses recorded from the dentate gyrus in hippocampal brain slices from temporal lobe epileptic patients. The field response to hilar stimulation was identical in both strains and was composed of a single population spike before and after bicuculline exposure. Mossy fiber terminals were not present in the molecular layer of either strain. We propose that the mechanisms leading to a greater likelihood of paroxysmal discharge generation in EL mouse may be important in the development and/or generation of epileptic seizures in this mouse strain and may be a significant phenotypic difference between the EL mouse and its parent strain.
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PMID:Paroxysmal discharges in the EL mouse, a genetic model of epilepsy. 923 45

This study examines forms of activity-dependent synaptic plasticity in the basolateral amygdala in vitro and demonstrates that a brief high frequency stimulus (HFS) train can induce a switch in the direction of the enduring change in synaptic strength induced by subsequent low-frequency stimulation (LFS). LFS (1 Hz, 15 min) of the external capsule (EC) induced a persistent 1.7-fold enhancement in the amplitude of synaptic potentials recorded intracellularly in basolateral amygdala neurons. The enhancement occurred gradually during the stimulation and was maintained for >30 min after termination of the stimulus train. LFS-induced enduring synaptic facilitation was not affected by the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoate (APV; 100 microM). Brief high-frequency EC stimulation (HFS; 100 Hz, 1 sec) induced APV-sensitive short-term potentiation (2.5-fold) that generally decayed within 10 min. When LFS was applied after recovery from the short-term potentiating effect of HFS (HFS/LFS), there was an initial transient (<10 min) enhancement of the synaptic response followed by persistent synaptic depression (synaptic potential amplitude reduced by 22% at 30 min). This represents the first demonstration of stimulus-dependent long-lasting synaptic depression in the amygdala. Application of the presynaptic (group II) metabotropic glutamate receptor antagonist 2S-alpha-ethylglutamic acid (EGLU; 50 microM) prevented the HFS-dependent switch from synaptic facilitation to depression. Thus, LFS in the in vitro amygdala slice can induce either enduring synaptic potentiation or depression, depending on whether a priming HFS train has been applied. This experience-dependent switch, a novel form of metaplasticity, is not dependent on NMDA receptors but may require group II metabotropic glutamate receptors. In the amygdala, experiential modification of activity-dependent long-term synaptic plasticity adds flexibility to the ways in which synaptic strength can be modified and could play a role in diverse amygdala-dependent processes, including the formation, storage, and extinction of emotional memory and the regulation of epileptogenesis.
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PMID:Bidirectional synaptic plasticity in the rat basolateral amygdala: characterization of an activity-dependent switch sensitive to the presynaptic metabotropic glutamate receptor antagonist 2S-alpha-ethylglutamic acid. 946 91

The action of histamine (HA) on rat hippocampal CA1 pyramidal cells in vitro was investigated in slices perfused with solution containing 0.2 mM Ca2+/4.0 mM Mg2+. Extracellular recordings of the spontaneous discharges occurring under these conditions revealed that HA caused a long-lasting increase in cell firing. The HA-effects were dose-dependent, in that low concentrations of HA (0.1-0.5 microM) exhibited an initial transient depression of cell firing and practically no long-lasting action, whereas higher concentrations of HA (1-10 microM) exerted strong, non-declining increases. The H1-receptor antagonist mepyramine (1 microM) blocked the initial depression of firing and attenuated the long-lasting HA-mediated excitation. Pure H1-receptor activation, tested with the H1-receptor agonist 2-(3-fluorphenyl)histamine (1-10 microM) depressed cell firing, similar to the low dose effects of HA. HA-induced excitations were prevented by the H2-receptor antagonist cimetidine (10-50 microM), and mimicked by the very potent H2-receptor agonist impromidine (1 or 3 microM) which was, however, less effective compared to equal concentrations of HA. H3-receptor activation by R-alpha-methylhistamine had no significant effect on cell firing. Thus, histamine H1 and H2 receptors seem to cooperate in producing this long-lasting augmentation of excitability. 8-Bromo-cyclic AMP monophosphate (8-Br-cAMP, 50-100 microM) mimicked the long-term excitation, whereas the adenylyl-cyclase inhibitor 9-tetrahydro-2-furyladenine (THFA, 100-500 microM) or the PKA-inhibitor Rp-adenosine-3'5'-cyclic monophosphate (Rp-cAMPS, 10 microM) blocked it, indicating that the HA-mediated increase of excitability in the hippocampus is dependent on the adenylate cyclase/PKA-signal transduction cascade. DL-2-Amino-5-phosphonopentanoic acid (APV, 50 microM) significantly attenuated the magnitude of the HA-induced enhancement, indicating an NMDA receptor-dependent component. Other biogenic amines, acting through receptors positively coupled to adenylyl cyclase, elicited similar responses as HA, indicating common mechanisms by which these substances modulate excitability in CA1 pyramidal cells.
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PMID:Long-term increase of hippocampal excitability by histamine and cyclic AMP. 951 24

General anesthetics are thought to depress the central nervous system (CNS) by acting at synapses; however, only a few studies have compared effects on axonal conduction with effects on synaptic responses using mammalian CNS preparations. The present study used glutamate receptor antagonists (CNQX/APV) or low calcium to block synaptic transmission, allowing Schaffer-collateral axon fiber volleys to be recorded from rat hippocampal brain slices. Since fiber volleys are compound action potentials, they provide a measure of axonal conduction in Schaffer-collateral fibers. Clinical concentrations of the inhalational anesthetic, halothane (1 rat MAC, 1.2 vol.%), produced an 18 +/- 2.3% depression of fiber volley amplitudes (mean +/- S.D.; p < 0.001 ANOVA, n = 10). Depression of action potential conduction accounted for approximately 30% of the overall depression of synaptic transmission produced by halothane at this concentration. Halothane-induced fiber volley depression occurred with little change in conduction velocity, similar to the effect seen with decreased stimulus intensity, but significantly different from the decreased velocity produced by tetrodotoxin (100 nM, p < 0.005). The results indicate that halothane can depress axonal conduction at clinically relevant concentrations and that this depression could contribute to the CNS depression that is associated with anesthesia.
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PMID:Halothane depresses action potential conduction in hippocampal axons. 968 73

Long-term potentiation (LTP) of spinal C-fibre-evoked field potentials can be induced by brief electrical stimulation of afferent C-fibres, by natural noxious stimulation of skin or by acute nerve injury. Here, we report that in urethane anaesthetized, adult rats prolonged high frequency burst stimulation of the sciatic nerve at Adelta-fibre strength produced long-term depression (LTD) of C-fibre-evoked field potentials, and also depressed the increased amplitudes of C-fibre-evoked field potentials recorded after LTP had been established (depotentiation). Electrical stimulation of Abeta-fibres failed to induce LTD or depotentiation. In spinalized rats, prolonged Adelta-fibre conditioning stimulation induced LTP rather than LTD of C-fibre-evoked field potentials. Thus, tonic descending inhibition may determine the direction of plastic changes in C-fibre-mediated synaptic transmission. Spinal application of the N-methyl-D-aspartic acid receptor antagonist D-APV blocked induction of LTD in intact rats and LTP in spinalized rats. The presently described LTD and the depotentiation of established LTP of C-fibre-evoked field potentials in spinal dorsal horn may underlie some forms of prolonged analgesia induced by peripheral nerve stimulation procedures.
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PMID:Long-term depression of C-fibre-evoked spinal field potentials by stimulation of primary afferent A delta-fibres in the adult rat. 978 1

The contribution of the cytoskeletal membrane-associated protein dystrophin in glutamatergic transmission and related plasticity was investigated in the hippocampal CA1 area of wild-type and dystrophin-deficient (mdx) mice, using extracellular recordings in the ex vivo slice preparation. Presynaptic fiber volleys and field excitatory postsynaptic potentials (fEPSPs) mediated through N-methyl-D-Aspartate receptors (NMDAr) or non-NMDAr were compared in both strains. Comparable synaptic responses were observed in wild-type and mdx mice, suggesting that basal glutamatergic transmission is not altered in the mutants. By contrast, the synaptic strengthening induced by a conditioning stimulation of either 10, 30, or 100 Hz was significantly greater in mdx mice during the first minutes posttetanus. Because the posttetanic potentiation induced in the presence of the NMDAr antagonist D-APV was not affected in the mutants, a critical role of NMDAr in this increase was suggested. The magnitude of the potentiation induced by a 30 Hz stimulation in mdx mice was normalized as compared to wild-type mice by increasing the extracellular magnesium concentration from 1.5 to 3 mM. Moreover, the transitory depression of fEPSPs induced by bath-applied NMDA (50 microM for 30s) was more sensitive to an increased extracellular magnesium concentration in wild-type than in mdx mice. Our results suggest that the absence of dystrophin may facilitate NMDAr activation in the CA1 hippocampal subfield of mdx mice, which may be partly due to a reduction of the voltage-dependent block of this receptor by magnesium.
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PMID:Facilitated NMDA receptor-mediated synaptic plasticity in the hippocampal CA1 area of dystrophin-deficient mice. 1038 Aug 51


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