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

The two forms of long-term potentiation (LTP) and one form of long-term depression (LTD) in hippocampal area CA1 are induced by different afferent tetani: LTD is induced by a 3- to 5-Hz tetanus, whereas higher frequencies are necessary for LTP mediated by NMDA receptors (25- to 50-Hz tetanus) and LTP mediated by voltage-dependent calcium channels (200-Hz tetanus). It has been suggested that the three forms are induced by graded increases in postsynaptic calcium, with LTD being induced at the lowest calcium concentration. We hypothesized that synapses near a site of LTP induction would elicit LTD owing to diffusion of calcium or its binding proteins. This was tested using a fixed multistimulating electrode array spanning stratum radiatum in area CA1 of rat hippocampal slices. The tetanized sites all displayed LTP. Nontetanized sites displayed LTD following a 50-Hz tetanus, whereas LTD was often seen following a 200-Hz tetanus. In most instances pEPSP and population spike responses were similar; however, EPSP/spike dissociations (LTD of EPSP, LTP of spike) were seen following activation of NMDA receptors by 50-Hz and 200-Hz tetani. The results are discussed with respect to mechanisms of action and functional significance.
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PMID:Long-term potentiation induces synaptic plasticity at nontetanized adjacent synapses. 1045 81

Long-term depression (LTD) of synaptic efficacy at CA1 synapses is believed to be a Ca(2+)-dependent process. We used high-speed fluorescence imaging and patch-clamp techniques to quantify the spatial distribution of changes in intracellular Ca2+ accompanying the induction of LTD at Schaffer collateral synapses in CA1 pyramidal neurons. Low-frequency stimulation (3 Hz), which was subthreshold for action potentials, produced small changes in [Ca2+]i and failed to elicit LTD. Increasing the stimulus strength so that action potentials were generated produced both robust LTD and increases in [Ca2+]i. Back-propagating action potentials at 3 Hz in the absence of synaptic stimulation also produced increases in [Ca2+]i, but failed to induce LTD. When subthreshold synaptic stimulation was paired with back-propagating action potentials, however, large increases in [Ca2+]i were observed and robust LTD was induced. The LTD was blocked by the N-methyl-D-aspartate receptor (NMDAr) antagonist APV, and stimulus-induced increases in [Ca2+]i were reduced throughout the neuron under these conditions. The LTD was also dependent on Ca2+ influx via voltage-gated Ca2+ channels (VGCCs), because LTD was severely attenuated or blocked by both nimodipine and Ni2+. These findings suggest that back-propagating action potentials can exert a powerful control over the induction of LTD and that both VGCCs and NMDArs are involved in the induction of this form of plasticity.
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PMID:The role of dendritic action potentials and Ca2+ influx in the induction of homosynaptic long-term depression in hippocampal CA1 pyramidal neurons. 1045 86

A neural network model of opponent cerebellar learning for arm movement control is proposed. The model illustrates how a central pattern generator in cortex and basal ganglia, a neuromuscular force controller in spinal cord, and an adaptive cerebellum cooperate to reduce motor variability during multijoint arm movements using mono- and bi-articular muscles. Cerebellar learning modifies velocity commands to produce phasic antagonist bursts at interpositus nucleus cells whose feed-forward action overcomes inherent limitations of spinal feedback control of tracking. Excitation of alpha motoneuron pools, combined with inhibition of their Renshaw cells by the cerebellum, facilitate movement initiation and optimal execution. Transcerebellar pathways are opened by learning through long-term depression (LTD) of parallel fiber-Purkinje cell synapses in response to conjunctive stimulation of parallel fibers and climbing fiber discharges that signal muscle stretch errors. The cerebellar circuitry also learns to control opponent muscles pairs, allowing cocontraction and reciprocal inhibition of muscles. Learning is stable, exhibits load compensation properties, and generalizes better across movement speeds if motoneuron pools obey the size principle. The intermittency of climbing fiber discharges maintains stable learning. Long-term potentiation (LTP) in response to uncorrelated parallel fiber signals enables previously weakened synapses to recover. Loss of climbing fibers, in the presence of LTP, can erode normal opponent signal processing. Simulated lesions of the cerebellar network reproduce symptoms of cerebellar disease, including sluggish movement onsets, poor execution of multijoint plans, and abnormally prolonged endpoint oscillations.
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PMID:A neural model of cerebellar learning for arm movement control: cortico-spino-cerebellar dynamics. 1045 12

This study is aimed at testing the hypothesis that sustained phosphorylation underlies long-term desensitization of AMPA receptors, which is thought to be the mechanism of long-term synaptic depression in cerebellar Purkinje cells (PCs). We induced long-term desensitization of AMPA receptors in rat cerebellar slices by (1) a 4-min bath application of quisqualate (0.1 mM) or (2) a 15-min bath application of a protein kinase C (PKC) activator, phorbol-12,13-diacetate (0.5 microM) or -dibutyrate (0.6 microM), followed by a 4-min AMPA (0.1 mM) application. In slices so treated, labeling with an antibody (12P3) against a peptide corresponding to part of AMPA receptor subunit GluR2 including serine 696 and phosphorylated at this serine site revealed phosphorylation of the AMPA receptors in PC dendrites that was sustained for at least 1 hr. At an early phase, within 20 min after the chemical stimulation, the phosphorylation was resistant to an Ca2+ chelator (BAPTA-AM), a metabotropic glutamate receptor antagonist (MCPG), and a PKC inhibitor (calphostin C), whereas at a late phase, 30 min or more after the chemical stimulation, it was blocked by these reagents similarly to long-term desensitization of AMPA receptors. Taken together with data obtained previously using different protocols of chemical stimulation, the present results strongly support the above-mentioned hypothesis.
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PMID:Persistent phosphorylation parallels long-term desensitization of cerebellar purkinje cell AMPA-type glutamate receptors. 1045 18

Recent evidence suggests that slowly propagating Ca2+ waves from astrocytes can modulate the function of neurons. Altering astrocytic calcium processes in vivo may therefore affect neuronal and behavioral phenotypes. Previously, we generated transgenic mice that overexpress an astrocytic calcium-binding protein, S100 beta. Immunocytochemistry and in situ hybridization showed elevated expression in the astrocytes of the hippocampus and other brain regions. Neurons in the hippocampus were negative for S100 beta. In this paper we analyze the hippocampal electrophysiology and learning properties of mice from two transgenic lines. Significant differences were found between the hippocampal slices of normal and transgenic mice in their response to high frequency (100 Hz) stimulation. The overall distribution of post-tetanic excitatory postsynaptic potentials (EPSP) of the slices from the transgenic mice was shifted significantly toward smaller values to a degree that 25% of slices exhibited depression. The altered hippocampal neurophysiology was accompanied by an impairment in a hippocampal-dependent learning task. Transgenic mice showed significant impairment in a spatial version of the Morris water maze, however, they performed normally in non-spatial tasks. Probe trials showed that transgenic mice, though significantly impaired, also acquired spatial information. The results suggested that the impairment was not due to motor dysfunction, impaired vision or motivation of the transgenic mice, findings compatible with a possible hippocampal mechanism. We conclude that overexpression of S100 beta in astrocytes impairs, but does not abolish, the ability to solve a spatial task, and it leads to a significantly decreased post-tetanic potentiation in the hippocampal slice. We hypothesize that the changes are due to calcium mediated processes. Our results support the notion that astrocytes are involved in higher brain functions.
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PMID:Overexpression of a calcium-binding protein, S100 beta, in astrocytes alters synaptic plasticity and impairs spatial learning in transgenic mice. 1046 64

The phenomenon of cerebellar long-term depression (LTD), a decrease of synaptic strength between the parallel fibers (PFs) and Purkinje cells after conjunctive activation of PFs and the climbing fibers (CFs), is implicated as a cellular mechanism for motor learning. We have characterized a field-potential recording technique in cerebellar slice and have used the technique to examine the temporal conditions for cerebellar LTD induction in an attempt to examine the relevance of LTD to associative conditioning. Interstimulus intervals (ISIs) between onsets of PF and CF activation and the number of paired stimuli (pairings) were examined. LTD has distinct temporal specificity that seems to be constrained by inhibitory interneurons and can be masked by excessive stimulation. When 100 paired stimuli were given to PFs and CFs, LTD was induced with an ISI of 250 msec (PF activation preceding CF activation). In contrast, a smaller forward (125 msec), simultaneous (0 msec), or backward (-250 msec) ISIs were not effective for inducing LTD. However, the blockade of GABAA receptor-mediated inhibition made it possible to induce LTD with 100 pairs of simultaneous stimulations. Furthermore, by increasing the number of pairings to 600, significant LTD was observed with all four interstimulus intervals. These results suggest that temporal conditions for LTD induction share some similarity to associative learning of discrete motor responses.
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PMID:Temporal specificity of long-term depression in parallel fiber--Purkinje synapses in rat cerebellar slice. 1046 75

In cerebellar long-term depression (LTD), conjunctive stimulation of parallel fiber (PF) and climbing fiber (CF) inputs to a Purkinje neuron result in a selective depression of PF-Purkinje neuron synaptic strength. This system is attractive for the study of neuronal information storage, both because of its duration and because it demonstrates input specificity. The mechanisms underlying input specificity in this system are not known, but they could involve presynaptic alterations, postsynaptic alterations, or some combination of both. To allow for an unambiguous analysis of postsynaptic processes, an LTD induction protocol has been developed using cultured cerebellar cells in which pulses of quisqualate and direct Purkinje neuron depolarization replace PF and CF stimulation, respectively. Input specificity is retained in this reduced system. When multiple, nonoverlapping quisqualate application sites are used, LTD is confined to those sites that are stimulated during depolarization. This property of LTD induction is also preserved under conditions where both spontaneous and evoked neurotransmitter releases are reduced or eliminated, indicating that postsynaptic alterations are sufficient to confer input specificity. Input-specific LTD may also be induced by local application of a protein kinase C (PKC) activator (1-oleoyl-2-acetylglycerol) together with direct Purkinje neuron depolarization, suggesting that input-specific LTD results from the conjunction of a spatially broad Ca signal mediated by Purkinje neuron depolarization, together with a spatially constrained PKC-activating signal mediated by quisqualate application.
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PMID:Input-specific induction of cerebellar long-term depression does not require presynaptic alteration. 1046 90

In the CA1 region of adult guinea pig hippocampal slices, long trains of theta frequency (5 Hz) stimulation produced a small enhancement of basal synaptic transmission but depressed the strength of synaptic transmission at synapses that had recently undergone long-term potentiation (LTP). Five hertz stimulation delivered immediately prior to high-frequency stimulation also inhibited the subsequent induction of LTP. The depression of potentiated synapses by 5 Hz stimulation (depotentiation) was blocked by 2-amino-5-phosphonovalerate and was observed only during the early phases of LTP. Furthermore, the protein phosphatase inhibitors okadaic acid and calyculin A blocked both depotentiation and the ability of 5 Hz stimulation to inhibit subsequent LTP, suggesting that protein phosphatases are involved in the ability of 5 Hz stimulation to modulate synaptic plasticity in the CA1 region of the hippocampus.
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PMID:Low-frequency stimulation erases LTP through an NMDA receptor-mediated activation of protein phosphatases. 1046 91

Long-term desensitization of AMPA receptors (LTDA) is a core mechanism of long-term depression, a model of motor learning in the cerebellum. In this study we investigated the expression of neurotrophic factor genes after induction of LTDA in cultured cerebellar slices. LTDA was induced by application of quisqualate and monitored as a population response with a wedge recording technique. The levels of mRNA were quantified by reverse transcription followed by polymerase chain reaction. Quisqualate, at a dose and duration that reliably induced LTDA, elicited a significant and specific increase in BDNF mRNA with a peak at four hours after the application. By cell fractionation, the major source of BDNF mRNA increase was found to be in granule cells. In addition, a small but significant increase of transcripts with specific exon usage was observed in a Purkinje cell fraction. These results indicate that BDNF may be coinduced with LTDA and suggest that the slow and sustained increase of BDNF mRNA might play a role in later phases of synaptic plasticity in the cerebellum.
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PMID:A stimulus paradigm inducing long-term desensitization of AMPA receptors evokes a specific increase in BDNF mRNA in cerebellar slices. 1046

Repetitive stimulation often results in habituation of the elicited response. However, if the stimulus is sufficiently strong, habituation may be preceded by transient sensitization or even replaced by enduring sensitization. In 1970, Groves and Thompson formulated the dual-process theory of plasticity to explain these characteristic behavioral changes on the basis of competition between decremental plasticity (depression) and incremental plasticity (facilitation) occurring within the neural network. Data from both vertebrate and invertebrate systems are reviewed and indicate that the effects of depression and facilitation are not exclusively additive but, rather, that those processes interact in a complex manner. Serial ordering of induction of learning, in which a depressing locus precedes the modulatory system responsible for inducing facilitation, causes the facilitation to wane. The parallel and/or serial expression of depression and waning facilitation within the stimulus-response pathway culminates in the behavioral changes that characterize dual-process learning. A mathematical model is presented to formally express and extend understanding of the interactions between depression and facilitation.
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PMID:Interactions between depression and facilitation within neural networks: updating the dual-process theory of plasticity. 1048 61


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