SEARCH · Search PubMed

Results for “synaptic plasticity”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 361 records · Page 20Linked to original sources

PubMed1999

Correlations between electrophysiological observations of synaptic plasticity modifications and behavioral performance in mammals.

Within the past century it has been well established that most mature neurons lose their ability to divide. Since then, it has been assumed that behavioral performance leads to synaptic changes in the brain. The existence of these potential changes has been demonstrated in numerous experiments, and different mechanisms contributing to synaptic plasticity have been discovered. Many structures involved in different types of learning have now been identified. This article reviews the different methods used with mammals to detect electrophysiological modifications in synaptic plasticity following behavior. Evidence of long-term potentiation and long-term depression has been found in the hippocampus and cerebellum, respectively, and empirical data has been used to correlate these mechanisms with specific learning performance. Similar observations were made recently in the septum and amygdala. These phenomena seem to be involved in maintaining the performance in the cortical areas of the brain. Ongoing attempts to find the relationship between behavioral performance and modifications in synaptic efficacy allow to speculate upon the dynamics of cellular mechanisms that contribute to the ability of mammals to modify wide neuronal networks in the brain during their life.

Animals↗

PubMed1986

Synaptic plasticity in vitro: cell culture of identified Aplysia neurons mediating short-term habituation and sensitization.

The gill withdrawal reflex of the marine mollusk, Aplysia californica, shows habituation and sensitization, two simple forms of learning. In order to extend the cellular studies on synaptic plasticity underlying the changes in the reflex behavior, and to explore further the development of synaptic plasticity during synapse formation, we have sought to establish the neural circuit of the gill withdrawal reflex in vitro. We report here the reconstruction of the elementary gill withdrawal circuit in cell culture and find that the cells show short-term homosynaptic depression and heterosynaptic facilitation, the cellular mechanisms of habituation and sensitization, respectively.

Action Potentials↗

PubMed2005

Synaptic plasticity at hippocampal mossy fibre synapses.

The dentate gyrus provides the main input to the hippocampus. Information reaches the CA3 region through mossy fibre synapses made by dentate granule cell axons. Synaptic plasticity at the mossy fibre-pyramidal cell synapse is unusual for several reasons, including low basal release probability, pronounced frequency facilitation and a lack of N-methyl-D-aspartate receptor involvement in long-term potentiation. In the past few years, some of the mechanisms underlying the peculiar features of mossy fibre synapses have been elucidated. Here we describe recent work from several laboratories on the various forms of synaptic plasticity at hippocampal mossy fibre synapses. We conclude that these contacts have just begun to reveal their many secrets.

Animals↗

PubMed2005

Repetitive paired-pulse TMS at I-wave periodicity markedly increases corticospinal excitability: a new technique for modulating synaptic plasticity.

OBJECTIVE: We hypothesised that facilitatory I-wave interaction set up by paired-pulse transcranial magnetic stimulation delivered with I-wave periodicity (iTMS) may reinforce trans-synaptic events and provide a means for modulating synaptic plasticity and cortical excitability. Our objective was to determine whether prolonged iTMS can increase corticospinal excitability, and whether this form of stimulation can have lasting aftereffects. METHODS: Paired stimuli of equal strength with a 1.5 ms inter-stimulus interval were delivered for 30 min at a rate of 0.2 Hz. Motor threshold and motor evoked potential (MEP) amplitude to single-pulse TMS was compared before and after intervention. RESULTS: Paired-pulse MEP amplitude increased linearly throughout the period of iTMS, and had increased five-fold by the end of the stimulation period. Single-pulse MEP amplitude was increased a mean of four-fold for 10 min after stimulation. Motor threshold was unaffected. CONCLUSIONS: iTMS is an effective method for increasing excitability of the human motor cortex, and probably acts by increasing synaptic efficacy. SIGNIFICANCE: Reinforcement of trans-synaptic events by iTMS may provide a means to investigate and modulate synaptic plasticity in the brain.

Adult↗

PubMed2002

New life in an old idea: the synaptic plasticity and memory hypothesis revisited.

The notion that changes in synaptic efficacy underlie learning and memory processes is now widely accepted, although definitive proof of the synaptic plasticity and memory hypothesis is still lacking. This article reviews recent evidence relevant to the hypothesis, with particular emphasis on studies of experience-dependent plasticity in the neocortex and hippocampus. In our view, there is now compelling evidence that changes in synaptic strength occur as a consequence of certain forms of learning. A major challenge will be to determine whether such changes constitute the memory trace itself or play a less specific supporting role in the information processing that accompanies memory formation.

Animals↗

PubMed1987

Primary structure and mRNA localization of protein F1, a growth-related protein kinase C substrate associated with synaptic plasticity.

Protein F1 is a neuron-specific, synaptic-enriched, membrane-bound substrate of protein kinase C (PKC) whose phosphorylation is related to synaptic plasticity in the adult. The sequence of 26 N-terminal amino acids was determined from purified rat protein F1. A 78-mer synthetic oligonucleotide designed from the partial N-terminal sequence enabled identification of protein F1 cDNA clones in a rat brain library. F1 protein is a 226 amino acid protein encoded by a 1.5 kb brain-specific, developmentally-regulated mRNA. Transcripts for protein F1 can be detected at birth, and their level declines after maturation. A full-length cDNA clone was transcribed and translated in vitro. Translation products could be immunoprecipitated with anti-F1 antibodies. In situ hybridization analysis revealed protein F1 transcripts in hippocampal pyramidal cells, but not in granule cells. In cerebellum, granule cells contained protein F1 mRNA, while Purkinje cells did not. Co-localization of protein F1 with protein kinase C-II [PKC-II (beta)], rather than PKC-I (gamma) suggests that PKC-II may phosphorylate protein F1.

Amino Acid Sequence↗

PubMed2003

Ubiquitination, protein turnover, and long-term synaptic plasticity.

For at least half a century, alteration of synaptic strength through growth at specific nerve terminals has been favored as the mechanism underlying long-term changes in behavior and synaptic plasticity. Although new proteins for synapses can either be synthesized locally or transported from the cell body, recent work on the postsynaptic element (dendritic spines) of cortical excitatory synapses indicates that transmission can also be modified by controlling the density of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptors (AMPARs) in the postsynaptic density (PSD). This regulation is mediated by mono-ubiquitination, which governs turnover of AMPAR subunits by determining whether the endocytosed subunits are sent to lysosomes to be degraded or recycled back to the membrane by exocytosis. Also important is activity-dependent multi-ubiquitination and degradation of proteins that make up the scaffolding complexes that confine receptors to the PSD.

Animals↗

PubMed2005

The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity, and memory in the hippocampus.

Long-lasting synaptic plasticity and memory requires mRNA translation, yet little is known as to how this process is regulated. To explore the role that the translation repressor 4E-BP2 plays in hippocampal long-term potentiation (LTP) and learning and memory, we examined 4E-BP2 knock-out mice. Interestingly, genetic elimination of 4E-BP2 converted early-phase LTP to late-phase LTP (L-LTP) in the Schaffer collateral pathway, likely as a result of increased eIF4F complex formation and translation initiation. A critical limit for activity-induced translation was revealed in the 4E-BP2 knock-out mice because L-LTP elicited by traditional stimulation paradigms was obstructed. Moreover, the 4E-BP2 knock-out mice also exhibited impaired spatial learning and memory and conditioned fear-associative memory deficits. These results suggest a crucial role for proper regulation of the eIF4F complex by 4E-BP2 during LTP and learning and memory in the mouse hippocampus.

Animals↗

PubMed1991

Calcium, network activity, and the role of NMDA channels in synaptic plasticity in vitro.

Functionally effective neuronal circuits are constructed through a competitive process that requires patterned neuronal activity elicited by structured input from the environment. To explore the mechanisms of this activity-dependent synaptic restructuring, we have developed an in vitro preparation of mouse spinal cord neurons maintained in a 3-chambered cell-culture system. Sensory afferents that received chronic electrical stimulation for 3-5 d developed stronger synaptic connections than unstimulated afferents converging onto the same postsynaptic spinal cord neuron. Exposure to 100 microM DL-2-amino-5-phosphonovaleric acid (APV), an antagonist of the NMDA channel, during the stimulation period prevented the competitive advantage associated with electric stimulation. However, when APV was applied with a higher concentration of calcium (3 mM), activity-dependent synaptic plasticity was no longer inhibited by the NMDA receptor antagonist. This reversal of APV block of the plasticity was not impaired by reducing transmitter release with 3 mM magnesium (in addition to 3 mM calcium and APV). A suppressant effect of APV on spontaneous activity was observed, which was attributed to loss of the NMDA component of the EPSP. Activity-dependent plasticity was also blocked if spontaneous activity was suppressed with dilute tetrodotoxin (TTX; 5-10 nM), a dosage that reduces excitability of neurons but is insufficient to block sodium-dependent action potentials. These experiments bring into question how NMDA channel activation is involved in the processes of synaptic remodeling during development. The data suggest that postsynaptic activity is required for synaptic remodeling, but this activity need not involve NMDA receptor activation specifically for activity-evoked synaptic plasticity. Instead, the mechanism for plasticity appears to operate through calcium-dependent processes in general.

2-Amino-5-phosphonovalerate↗

PubMed2002

Facilitated CA1 hippocampal synaptic plasticity in dystrophin-deficient mice: role for GABAA receptors?

Duchenne muscular dystrophy (DMD) is associated with cognitive deficits that may result from a deficiency in the brain isoform of the cytoskeletal membrane-associated protein, dystrophin. CA1 hippocampal short-term potentiation (STP) of synaptic transmission is increased in dystrophin-deficient mdx mice, which has been attributed to a facilitated activation of NMDA receptors. In this study, extracellular recordings in the hippocampal slice preparation were used first to determine the consequences of this alteration on short-term depression (STD). STD induction was facilitated in mdx as compared with wild-type mice in a control medium. Because brain dystrophin deficiency results in a decreased number of gamma-aminobutyric acid A (GABAA)-receptor clusters, we tested the hypothesis that neuronal disinhibition contributes to the enhanced synaptic plasticity in mdx mice. We found that the GABAA receptor antagonist, bicuculline, increased basal neurotransmission in wild-type, but not in mdx mice and prevented the enhanced STP and STD in the CA1 area of slices from mdx mice. The possibility that altered GABA mechanisms underlie the facilitation of NMDA receptor-dependent synaptic plasticity in mdx mice is discussed.

Animals↗

PubMed1999

Hippocampal synaptic plasticity and cognition.

Discoveries made over the past 20 years have greatly improved our understanding of how the brain functions. This article focuses on the relation between memory and cellular mechanisms of neuronal and synaptic plasticity in the hippocampus. Several studies indicate that the hippocampal formation is a crucial element of the neurobiological bases of higher cognitive function. Severe damage to the hippocampal formation is known to produce seemingly permanent anterograde amnesia. A generally accepted hypothesis in neurobiology has been that long-lasting activity-dependent changes in the efficacy of synaptic transmission in the mammalian brain are considered to be of fundamental importance for the development of neural circuitry and for the storage of information. The most compelling and reliable model for such changes has been long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus. Therefore, the possibility of the discovery and development of compounds that, by modulating hippocampal synaptic plasticity, would be useful for the management of dementia and amnesia.

Amnesia↗

PubMed2006

In vivo synaptic plasticity in the dentate gyrus of mice deficient in the neural cell adhesion molecule NCAM or its polysialic acid.

The neural cell adhesion molecule NCAM and its associated polysialic acid (PSA) play important roles in synaptic plasticity in the CA1 and/or CA3 regions of the hippocampus in vitro. Here, we address the question of whether NCAM and PSA are involved in regulation of synaptic transmission and plasticity also in vivo at synapses formed by entorhinal cortex axons in the dentate gyrus of mice anaesthetized with urethane. We show that basal synaptic transmission, measured as the slope of field excitatory postsynaptic potentials, was reduced strongly in mice lacking ST8SiaII/STX, the enzyme involved in polysialylation of NCAM in stem cell-derived immature granule cells, but not in mice deficient either in the NCAM glycoprotein or the enzyme ST8SiaIV/PST involved in polysialylation of NCAM in mature neurons. Strikingly, only mice deficient in NCAM, but not in PST or STX, were impaired in long-term potentiation (LTP) induced by theta-burst stimulation, suggesting that LTP in the dentate gyrus depends on the NCAM glycoprotein alone rather than on its associated PSA. As also patterns of synaptic activity during and immediately after induction of LTP were impaired in NCAM-deficient mice, it is likely that induction of LTP requires NCAM. These data are the first to describe that NCAM is necessary for induction of synaptic plasticity in identified synapses in vivo and suggest that polysialylation of NCAM expressed by immature granule cells in the dentate gyrus supports development of basal excitatory synaptic transmission in this region.

Animals↗

PubMed2006

Enhanced group II mGluR-mediated inhibition of pain-related synaptic plasticity in the amygdala.

BACKGROUND: The latero-capsular part of the central nucleus of the amygdala (CeLC) is the target of the spino-parabrachio-amygdaloid pain pathway. Our previous studies showed that CeLC neurons develop synaptic plasticity and increased neuronal excitability in the kaolin/carrageenan model of arthritic pain. These pain-related changes involve presynaptic group I metabotropic glutamate receptors (mGluRs) and postsynaptic NMDA and calcitonin gene-related peptide (CGRP1) receptors. Here we address the role of group II mGluRs. RESULTS: Whole-cell current- and voltage-clamp recordings were made from CeLC neurons in brain slices from control rats and arthritic rats (>6 h postinjection of kaolin/carrageenan into the knee). Monosynaptic excitatory postsynaptic currents (EPSCs) were evoked by electrical stimulation of afferents from the pontine parabrachial (PB) area. A selective group II mGluR agonist (LY354740) decreased the amplitude of EPSCs more potently in CeLC neurons from arthritic rats (IC50 = 0.59 nM) than in control animals (IC50 = 15.0 nM). The inhibitory effect of LY354740 was reversed by a group II mGluR antagonist (EGLU) but not a GABAA receptor antagonist (bicuculline). LY354740 decreased frequency, but not amplitude, of miniature EPSCs in the presence of TTX. No significant changes of neuronal excitability measures (membrane slope conductance and action potential firing rate) were detected. CONCLUSION: Our data suggest that group II mGluRs act presynaptically to modulate synaptic plasticity in the amygdala in a model of arthritic pain.

Amygdala↗

PubMed2000

Unveiling synaptic plasticity: a new graphical and analytical approach.

Short-term synaptic plasticity has a key role in information processing in the CNS, whereas memories can be formed through long-lasting changes in synaptic strength. Despite the importance of these phenomena, it remains difficult to determine whether a synaptic modulation is expressed at a presynaptic or postsynaptic site. This article describes a new approach that, in its simplest form, can identify the site of expression by direct graphical means. A more-sophisticated form of the technique can quantify functional synaptic properties and determine which of these properties is altered following a modulation of synaptic strength.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2006

Opiate withdrawal modifies synaptic plasticity in subicular-nucleus accumbens pathway in vivo.

Subiculum receives output of hippocampal CA1 neurons and projects glutamatergic synapses onto nucleus accumbens (NAc), the subicular-NAc pathway linking memory and reward system. It is unknown whether morphine withdrawal influences synaptic plasticity in the subicular-NAc pathway. Here, we recorded the field excitatory postsynaptic potential (EPSP) within the shell of NAc by stimulating ventral subiculum in anesthetized adult rats. We found that high frequency stimulation (HFS, 200 Hz) induced long-term potentiation (LTP) but low frequency stimulation (LFS, 1 Hz) failed to induce long-term depression (LTD) in control animals. However, behavioral stress enabled LFS to induce a reliable LTD (sLTD) that was dependent on the glucocorticoid receptors. Both LTP and sLTD were prevented by the N-methyl-d-aspartate receptor antagonist AP-5. After repeated morphine treatment for 12 days, acute withdrawal (12 h) impaired LTP but had no effect on sLTD; prolonged withdrawal (4 days) restored the LTP but impaired the sLTD. Remarkably, basal synaptic efficacy reflected by baseline EPSP amplitude was potentiated in acute withdrawal but was depressed in prolonged withdrawal. Thus, acute and prolonged opiate withdrawal may cause endogenous LTP and LTD in the subicular-NAc pathway that occludes the subsequent induction of synaptic plasticity, demonstrating adaptive changes of the NAc functions during opiate withdrawal.

Animals↗

PubMed1999

Memory suppressor genes: enhancing the relationship between synaptic plasticity and memory storage.

Memory suppressor genes encode proteins that act as inhibitory constraints to impede memory storage. The study of memory suppressor genes is important not only for understanding the link between synaptic plasticity and learning but also for identifying potential targets for future pharmaceuticals to treat memory disorders. This article first reviews the evidence for proteins that impede memory storage from work in invertebrates and then explores recent evidence for the existence of memory suppressor genes in vertebrates in the context of hippocampus-dependent forms of memory. In Aplysia, memory suppressor gene products act at each step in long-term facilitation: in the cytoplasm to regulate kinase activity, in the nucleus to alter the activity of transcriptional regulatory proteins, and on the cell surface to modulate cell-cell interactions. Studies of genetically modified Drosophila have provided behavioral evidence for the existence of memory suppressor genes. One of the best candidates for a neuronal mechanism underlying learning is long-term potentiation (LTP), which has been extensively studied in the mammalian hippocampus. Recent work has identified a number of putative memory suppressor gene products that act in the hippocampus at the levels of LTP induction, regulation of intracellular signaling cascades, and transcriptional control. Using these gene products as tools to study enhancements rather than deficits in LTP and learning may generate more precise information about the relationship between synaptic plasticity and behavioral learning. The study of mammalian memory suppressor genes may provide insights into alleviating the learning and memory deficits that accompany both normal aging and a variety of human disorders.

Animals↗

PubMed2002

Changes in synaptic plasticity in the rat hippocampo-medial prefrontal cortex pathway induced by repeated treatments with fluvoxamine.

The present studies were conducted to examine the effects of single and repeated treatments with fluvoxamine, which is a selective serotonin reuptake inhibitor (SSRI), on the synaptic efficacy and synaptic plasticity in the rat hippocampo-medial prefrontal cortex (mPFC) pathway in vivo. It has been reported that the projections arising from the hippocampal structures to the mPFC are involved in the execution of higher cognitive functions in rats. The evoked potentials were recorded in the mPFC by stimulation of the CA1/subicular region of the ventral hippocampus in halothane-anesthetized rats. Single administration of fluvoxamine (10 and 30 mg/kg, i.p.) enhanced synaptic efficacy in the hippocampo-mPFC pathway in a dose-dependent manner. Although repeated treatments with fluvoxamine (30 mg/kg, i.p. after 30 mg/kg/dayx21 days, p.o.) caused an enhancement of synaptic efficacy, there was no significant difference between single and repeated treatments. The input/output characteristics showed hypersensitivity to stimulation intensity in the group with repeated fluvoxamine treatments. The establishment of long-term potentiation (LTP) in the hippocampo-mPFC pathway after a single administration of fluvoxamine was not different from that in the saline-injected group. On the other hand, the hippocampo-mPFC LTP was significantly augmented by repeated treatments with fluvoxamine when compared to a single treatment. These findings suggest that the serotonergic system could modulate the synaptic plasticity at hippocampal-mPFC synapses. The present study, furthermore, suggests that the enhancement of LTP in the hippocampo-mPFC pathway produced by repeated treatments with fluvoxamine may be implicated in the SSRI-induced therapeutic effect on psychiatric disorders.

Afferent Pathways↗

PubMed2001

The highly sialylated isoform of the neural cell adhesion molecule is required for estradiol-induced morphological synaptic plasticity in the adult arcuate nucleus.

The large quantities of polysialic acid (PSA) characterizing highly sialylated isoform of the neural cell adhesion molecule (PSA-NCAM), greatly reduce cell adhesion and render this particular cell surface adhesion molecule a likely candidate to intervene in dynamic neuronal phenomena, such as synaptic plasticity. The hypothalamic arcuate nucleus expresses high levels of PSA-NCAM and maintains a high capacity for neuroplastic changes in the adult. Thus, in the arcuate nucleus of female rats, varying circulating levels of estrogen give rise to a reversible reduction in the number of axo-somatic GABA synapses, together with a changing ensheathing of neuronal somata by astrocytes. To examine the role of PSA in such changes, we perturbed its expression, either by blockade with antibodies raised against this carbohydrate moiety (delivered intracerebroventricularly), or by its enzymatic cleavage after microinjection of endoneuraminidase N over the arcuate nucleus. Either procedure was performed in ovariectomized adult rats that received concurrent treatment with 17 beta-estradiol. Morphological synaptic plasticity was analysed using the unbiased disector method to assess synaptic densities in ultrathin sections of the arcuate nucleus immunogold-labelled for GABA. As expected, 17 beta-estradiol induced a significant reduction in the number of GABAergic axo-somatic synapses, a reduction which did not occur after infusion of anti-PSA antibodies or in vivo enzymatic removal of PSA from NCAM. Taken together, our results provide strong evidence that the presence of large quantities of the PSA moiety on NCAM is a necessary prerequisite for estrogen-induced phasic remodelling of synapses in the adult female arcuate nucleus.

Animals↗