Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Weak excitation to rat hippocampal CA1 neurons via Schaffer collaterals at a frequency of 0.1 or 0.2 Hz accompanied by repeated brief exposures to the inhibitory transmitter gamma-amino-butyric acid (GABA) causes a long-term depression (LTD, up to 90% of the control) of the stimulated pathway. This depression can be reversed by high-frequency stimulation. 2. Although inhibition is necessary for the induction of this LTD, the depression can be produced with either the GABAA or the GABAB receptor agonists. 3. This conjunctive LTD could not be blocked by the N-methyl-D-aspartate receptor antagonist, 2-amino-5-phosphonovaleric acid. 4. It was, however, blocked by the metabotropic glutamate receptor antagonist L-2-amino-3-phosphonopropionic acid and (RS)-alpha-methyl-4-carboxyphenylglycine, indicating that activation of a metabotropic glutamate receptor is necessary for the LTD. Induction also appeared to require an intracellular Ca2+ increase. 5. Because GABAergic inhibition often modulates glutamatergic transmission in the brain, we propose that this form of synaptic modification is of potential importance for neural plasticity.
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PMID:Weak excitation and simultaneous inhibition induce long-term depression in hippocampal CA1 neurons. 803 37

In rat cerebellar slices, 500 microM (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) reversibly inhibited both dendritic and somatic increases in FLUO-3 fluorescence intensity induced by bath applications of 50-100 microM (+-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD). No effect of MCPG was observed on dendritically recorded excitatory postsynaptic potentials evoked by synaptic activation of either parallel or climbing fibres. Long-term depression of parallel fibre-Purkinje cell transmission, induced either by conjunctive activation of parallel and climbing fibres or by pairing parallel fibre stimulation with intradendritic injections of 8-BrcGMP, was not only prevented in the presence of MCPG but a robust long-term potentiation of responses consistently occurred. These data show that metabotropic glutamate receptor activation is necessary for the induction of LTD.
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PMID:Induction of cerebellar long-term depression requires activation of glutamate metabotropic receptors. 806 Dec 95

1. To see whether there is a threshold of postsynaptic depolarization for induction of long-term potentiation (LTP) or depression (LTD) of synaptic transmission, perforated patch-clamp recordings were carried out under microscopic observation from 61 layer II/III neurons in visual cortical slices of young rats. Electrical stimulation given to nearby neurons was paired with stepwise shifts (30- or 300-ms duration) of clamped membrane potential of the recorded neurons to various levels. 2. Excitatory postsynaptic currents (EPSCs) were elicited by focal stimulation of a nearby pyramidal cell-like neuron. As the intensity of stimulation was increased, EPSCs emerged abruptly with 100% probability, and their peak latencies and amplitudes remained almost constant up to more than twice the threshold, indicating that the EPSCs were elicited monosynaptically. 3. LTP of EPSCs was induced in 11 of the 15 cells after pairing with a step to -20 mV and in 5 of the 14 cells after pairing with a step to -40 mV. No LTP was observed when the postsynaptic cells were clamped at -60, -70, or -90 mV. Significant LTD was not seen at any membrane potential level tested. There was no significant difference between the duration of potential shift of 30 and 300 ms during the pairing procedure in induction probability of LTP and magnitude of LTP, if it was induced. 4. These results suggest that LTP is induced by synaptic inputs associated with postsynaptic depolarization above the threshold around -40 mV at synapses linking layer II/III neurons in the developing visual cortex.
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PMID:Dependence of LTP induction on postsynaptic depolarization: a perforated patch-clamp study in visual cortical slices of young rats. 806 39

Age-related memory impairments may be due to dysfunction of the septohippocampal system. The medial septal area (MSA) provides the major cholinergic projection to the hippocampus and is critical for memory. Knowledge of the neurobiological mechanisms by which the cholinergic system can attenuate age-related memory loss can facilitate the development of effective cognitive enhancers. At present, one of the best neurobiological models of memory formation is long-term potentiation/long-term depression (LTP/LTD). In previous studies, intraseptal infusion of the muscarinic agonist oxotremorine, which excites MSA neurons, improved memory in aged rats. The present study examined LTP and LTD in aged Fisher 344 rats following intraseptal infusion of oxotremorine. LTP and LTD were assessed using the slope of the EPSP recorded from the hilar region of the dentate gyrus. Induction of LTP was blocked in the lateral perforant path, but not in the medial perforant path, following intraseptal infusions of oxotremorine. The generation and amplitude of heterosynaptic LTD was enhanced in the medial perforant path, but not in the lateral perforant path. The results provide evidence that pharmacological activation of the MSA can modulate LTP and LTD in the hippocampus of aged rats. The implications of these results with respect to memory and synaptic plasticity in the hippocampus are discussed.
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PMID:Activation of the medial septal area attenuates LTP of the lateral perforant path and enhances heterosynaptic LTD of the medial perforant path in aged rats. 814 24

Although long-term potentiation (LTP) has been demonstrated in a number of subcortical sites in chronic preparations, there have been no demonstrations of LTP in the neocortex of chronic preparations. Even neocortical slice and acute preparations often require a drug-induced suppression of inhibition before LTP effects can be reliably induced. We have attempted to induce LTP in neocortical sites in 7 different experiments using chronically prepared adult rats. We were unable to obtain any evidence, even a trend, for the induction of LTP. The following manipulations were tested: (1) standard stimulation train parameters that have been shown to be highly effective in subcortical and hippocampal sites; (2) a 10-fold increase in the intra-train pulse durations; (3) variations in train pulse frequency (1 Hz to 300 Hz) and train duration (100 ms to 15 min); (4) co-activation of multiple inputs by stimulation of combinations of cortical sites or cortical and thalamic sites; (5) reduction of inhibition by administration of picrotoxin; 5) Housing of animals in an enriched environment; (6) utilization of the neocortical stimulation trains as a cue in a learning task; (7) application of pilocarpine to co-activate cholinergic systems. Although none of these manipulations produced LTP, the application of pilocarpine did facilitate the induction of a long-lasting depression effect. These findings contrast with the results obtained from anesthetized rats and from studies using brain slices, where LTP can be reliably induced. These results are discussed in light of other recent findings with respect to LTP and LTD effects.
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PMID:Post-activation potentiation and depression in the neocortex of the rat: II. Chronic preparations. 818 Aug 23

The effects of the nonspecific cyclic nucleotide inhibitors 1-methyl-3-isobutylxanthine (IBMX) and dipyridamole, and the cGMP-specific phosphodiesterase inhibitor Zaprinast were studied on parallel fiber-Purkinje cell synaptic responses in rat cerebellar slices. Bath application of all three compounds, at concentrations shown to inhibit cGMP breakdown, led to stable and robust long-term depression of PF responses. Injections of dipyridamole directly into the Purkinje cell dendrites were similarly effective as bath applications, confirming a postsynaptic site of action. Inhibitors of both protein kinase G and C and also the metabotropic glutamate receptor antagonist MCPG completely prevented the induction of LTD by dipyridamole and Zaprinast. The extent of phosphodiesterase-induced synaptic depression was dependent on the frequency of parallel fiber stimulation, and this form of LTD both occluded and was occluded by LTD induced by pairing parallel and climbing fiber inputs. The degree of LTD induced by IBMX was dose-dependent, and also required PKC and PKG activity, but was preceded by a large, transient potentiation of parallel fiber responses occurring by a postsynaptic mechanism independent of cGMP. These data not only confirm that cGMP is capable of inducing cerebellar LTD when paired with parallel fiber stimulation but indicate that cGMP is an endogenous intermediate in this form of synaptic plasticity.
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PMID:Inhibition of cGMP breakdown promotes the induction of cerebellar long-term depression. 862 19

The neocortex is an important site of memory storage, and memories are believed to be formed in the cortex by the activity-dependent modification of synaptic connections. However, in contrast to the hippocampus where there has been an increasingly sophisticated analysis of synaptic plasticity, relatively little is known about the mechanisms of synaptic modification in neocortex. Here we summarize the results of a series of experiments conducted on slices of visual cortex in vitro, aimed at elucidating the elementary mechanisms of synaptic plasticity in the superficial layers of neocortex. We show that long-term potentiation (LTP) and depression (LTD) result from high- and low-frequency conditioning stimulation, respectively, of the middle layers of cortex. Both forms of synaptic plasticity are input-specific and dependent on activation of postsynaptic N-methyl-D-aspartate (NMDA) receptors. The critical variable in determining the sign of the synaptic modification appears to be the level of postsynaptic depolarization during conditioning stimulation. The data support a model in which the state of correlation of pre- and post-synaptic activity is converted by the voltage-dependent NMDA receptor channel into a graded postsynaptic Ca2+ signal. LTD is triggered by a modest but sustained elevation in postsynaptic Ca2+, while LTP is elicited by larger changes in Ca2+. An important variable that regulates synaptic plasticity in the neocortex is intracortical inhibition, which constrains the patterns of activity that can reach the modifiable synapses in layer III.
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PMID:Elementary forms of synaptic plasticity in the visual cortex. 872 22

As previously demonstrated, high frequency stimulation (HFS) of the primary vestibular afferents always induces a clear, long lasting depression of the polysynaptic (N2) component of the field potentials recorded in the dorsal portion of the medial vestibular nuclei (MVN). The induction of the HFS effect was mediated by the activation of glutamate NMDA receptors, since it was blocked by AP5. The mechanisms at the basis of such a depression were studied. Our results demonstrate that Gaba, acting on both GabaA and GabaB receptors, is involved in mediating this phenomenon. In fact, HFS applied during Bicuculline and Saclofen perfusion, was no longer able to induce an N2 depression, but provoked a slight potentiation. However, the N2 depression clearly emerged after drug wash-out. Furthermore, Bicuculline and Saclofen fully abolished the N2 depression and highlighted the potentiation, when administered after HFS. The possibility that the N2 depression is the result of a homosynaptic LTD can be excluded on the basis of our results. On the contrary, our findings suggest that the depression is due to an enhancement of the Gaba inhibitory effect due to an HFS dependent increase in gabaergic interneuron activity, which resets vestibular neuron excitability at a lower level.
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PMID:Gaba mediated long-term depression (LTD) in the rat medial vestibular nuclei. 874 9

The temporal and spatial changes in intracellular calcium levels during separate activation of parallel fiber (PF) and climbing fiber (CF) inputs to cerebellar Purkinje cells were studied. PF stimulation (1 Hz), at relatively high stimulus strengths, led to accumulations of calcium that were similar in peak levels to those following CF stimulation but that remained spatially localized. Such stimuli consistently induced a durable depression of PF synaptic transmission that partially occluded further depression by conventional conjunctive stimuli and that was independent of nitric oxide. This depression was accompanied by a reduction of synaptic efficacy in spatially isolated PF inputs to the same cell that was independent of postsynaptic calcium but that was mediated by nitric oxide. These data indicate that LTD comprises at least two separate processes and that parameters of PF stimulation that are capable of raising calcium levels in Purkinje cell dendrites are also able to induce long-term changes in synaptic efficacy.
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PMID:Strong activation of parallel fibers produces localized calcium transients and a form of LTD that spreads to distant synapses. 878 57

S100 beta, a calcium binding brain protein expressed by astrocytes, has been shown to be involved in higher neural processes, including hippocampal-dependent behavioral traits and hippocampal neuronal long-term potentiation (LTP) and depression (LTD), neurophysiological phenomena that may be involved in exploring, learning and remembering novel stimuli. In the present study, the exploratory behavior of previously generated transgenic mice overexpressing the protein are compared to that of normal control mice of identical genetic background and age in a T-maze. The test mice encountered a normal control and an S100 beta transgenic mouse (the choice mice) in the goal arms of the T-maze. We show that no test mice exhibited any preference for either genotype of choice mouse. However, there was a significant difference in the spatial and temporal exploratory pattern between control and S100 beta test mice, demonstrating that S100 beta overexpression significantly altered the behavior of the transgenic mice. We suggest that one probable factor underlying the abnormalities observed is impaired short-term memory.
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PMID:Conspecific exploration in the T-maze: abnormalities in S100 beta transgenic mice. 880 39


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