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Results for “synaptic plasticity”

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At least 271 records · Page 15Linked to original sources
PubMed2003

Serotonin type II receptor activation facilitates synaptic plasticity via N-methyl-D-aspartate-mediated mechanism in the rat basolateral amygdala.

The modulation of synaptic plasticity by serotonin type II (5-hydroxytryptamine type II (5-HT(2)))-receptor stimulation was explored using intracellular, field potential and Fura-2 fluorescence image recordings in a rat amygdala slice preparation. Bath application of 5HT(2) receptor agonist 1-(2,5)-dimethoxy-4-iodophen-2-aminopropane (DOI) transformed theta-burst-stimulated (TBS) synaptic plasticity from short-term potentiation to long-term potentiation. DOI enhanced N-methyl-D-aspartate (NMDA) receptor-mediated potentials and calcium influx without affecting the resting membrane potential or input resistance of the neurons. In contrast, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate receptor-mediated excitatory synaptic responses were unaffected by DOI. The facilitating effects of DOI were blocked by the 5-HT(2) receptor antagonist, ketanserin, and by the 5-HT(2C)-receptor selective antagonist, RS102221. These results indicate that 5-HT(2)-receptor activation enhances NMDA receptor-mediated synaptic function in the basolateral amygdala (BLA).

Amygdala↗
PubMed2004

The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition.

A diet high in saturated fat (HF) decreases levels of brain-derived neurotrophic factor (BDNF), to the extent that compromises neuroplasticity and cognitive function, and aggravates the outcome of brain insult. By using the antioxidant power of vitamin E, we performed studies to determine the role of oxidative stress as a mediator for the effects of BDNF on synaptic plasticity and cognition caused by consumption of the HF diet. Male adult rats were maintained on a HF diet for 2 months with or without 500 IU/kg of vitamin E. Supplementation of the HF diet with vitamin E dramatically reduced oxidative damage, normalized levels of BDNF, synapsin I and cyclic AMP-response element-binding protein (CREB), caused by the consumption of the HF diet. In addition, vitamin E supplementation preserved the process of activation of synapsin I and CREB, and reversed the HF-impaired cognitive function. It is known that BDNF facilitates the synapse by modulating synapsin I and CREB, which have been implicated in synaptic plasticity associated to learning and memory. These results show that oxidative stress can interact with the BDNF system to modulate synaptic plasticity and cognitive function. Therefore, studies appear to reveal a mechanism by which events classically related to the maintenance of energy balance of the cell, such as oxidative stress, can interact with molecular events that modulate neuronal and behavioural plasticity.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1996

The corticostriatal projection: from synaptic plasticity to dysfunctions of the basal ganglia.

Corticostriatal transmission has an important function in the regulation of the neuronal activity of the basal ganglia. The firing activity of corticostriatal neurones excites striatal cells via the release of glutamate. Presynaptic receptors that are located on corticostriatal terminals and that regulate the release of glutamate in the striatum have been postulated for dopamine and glutamate. Activation of these receptors may exert a negative feed-back on the striatal release of glutamate. High-frequency activation of corticostriatal fibres causes either long-term depression or long-term potentiation of excitatory transmission depending on the subclass of glutamate receptor that is activated. These forms of synaptic plasticity could be involved in motor learning. Alterations in striatal synaptic plasticity might be implicated in Parkinson's disease and Huntington's disease.

Animals↗
PubMed2001

Cyclic changes in estradiol regulate synaptic plasticity through the MAP kinase pathway.

Hippocampal synaptic structure and function exhibit marked variations during the estrus cycle of female rats. Estradiol activates the mitogen-activated protein (MAP) kinase pathway in numerous cell types, and MAP kinase has been shown to play a critical role in the mechanisms underlying synaptic plasticity. Here, we report that endogenous estrogen produces a tonic phosphorylation/activation of extracellular signal-regulated kinase 2 (ERK2)/MAP kinase throughout the female rat brain and an increase in tyrosine phosphorylation of NR2 subunits of N-methyl-D-aspartate (NMDA) receptors. Moreover, cyclic changes in estrogen levels during the estrus cycle of female rats are associated with corresponding changes in the levels of activation of ERK2, the state of tyrosine phosphorylation of NR2 subunits of NMDA receptors, and the magnitude of long-term potentiation in hippocampus. Thus, cyclic changes in female sexual hormones result in marked variations in the state of activation of a major cellular signaling pathway critical for learning and memory and in a cellular model of learning and memory.

Animals↗
PubMed2002

Transgenic calmodulin-dependent protein kinase II activation: dose-dependent effects on synaptic plasticity, learning, and memory.

Genetic disruption of calmodulin-dependent protein kinase II (CaMKII) function alters hippocampal synaptic plasticity and memory in mice. We used transgenic mice carrying a tetracycline-regulated, calcium-independent form of CaMKII (CaMKII-Asp286) to investigate the role of CaMKII activation on synaptic plasticity and behavior. Mice expressing low levels of a CaMKII-Asp286 transgene have facilitated low-frequency (5 Hz)-induced long-term potentiation (LTP), whereas mice with high levels of transgene expression have a deficit in this form of plasticity. Behavioral impairments on fear-conditioned memory and visible water maze correlate with the level of CaMKII-Asp286 expression. Mice with high levels of CaMKII-Asp286 have reversible, compensatory changes in the expression of genes associated with inhibitory neurotransmission. These results demonstrate that in the hippocampus, CaMKII activation facilitates the induction of low-frequency LTP, but at high levels of expression, compensatory mechanisms act to inhibit the induction of this form of LTP. The most severe behavioral impairments are associated with activation of this compensatory mechanism.

Animals↗
PubMed2004

Spike timing and synaptic plasticity in the premotor pathway of birdsong.

The neural circuits of birdsong appear to utilize specific time delays in their operation. In particular, the anterior forebrain pathway (AFP) is implicated in an approximately 40- to 50- ms time delay, DeltaT, playing a role in the relative timing of premotor signals from the nucleus HVc to the nucleus robust nucleus of the archistratium (RA) and control/learning signals from the nucleus lateral magnocellular nucleus of the anterior neostratium (lMAN) to RA. Using a biophysical model of synaptic plasticity based on experiments on mammalian hippocampal and neocortical pyramidal neurons, we propose an understanding of this approximately 40- to 50- ms delay. The biophysical model describes the influence of Ca2+ influx into the postsynaptic RA cells through NMDA and AMPA receptors and the induction of LTP and LTD through complex metabolic pathways. The delay, DeltaT, between HVc --> RA premotor signals and lMAN --> RA control/learning signals plays an essential role in determining if synaptic plasticity is induced by signaling from each pathway into RA. If DeltaT is substantially larger than 40 ms, no plasticity is induced. If DeltaT is much less than 40 ms, only potentiation is expected. If DeltaT approximately 40 ms, the sign of synaptic plasticity is sensitive to DeltaT. Our results suggest that changes in DeltaT may influence learning and maintenance of birdsong. We investigate the robustness of this result to noise and to the removal of the Ca2+ contribution from lMAN --> RA NMDA receptors.

Action Potentials↗
PubMedDate not supplied

Synaptic plasticity is preserved in the temporal cortex of 20-month-old rats.

The molecular mechanisms associated with age-related alterations in the plasticity of the cortical neurons in response to chemically-induced seizure are largely unknown. Administration of pentylenetetrazole (PTZ) (50 mg/kg body weight) to rats of various ages evoked tonic-clonic seizures. Using immunoblotting and in situ hybridization analysis we found that 72 h after the onset of seizure, the mRNA for microtubule-associated protein 1B (MAP1B), a marker of synaptic plasticity, was increased in the cortex of 3-month-old rats. The levels of MAP1B mRNA in the cortex of 3-month-old rats returned to control levels by 10 days after PTZ administration. The levels of MAP1B mRNA in the hippocampus and cortex of 20 months at later times (10 days) and returned nearly to basal levels by 20 days following PTZ treatment. Immunohistochemical analysis revealed that MAP1B-like immunoreactivity was confined to layer II and neuronal processes extending into layer I. In contrast, the staining of MAP1B in the temporal cortex of 20-month-old animals was restricted to neuronal cell bodies of layer II. Since synaptic plasticity is associated mainly with neuronal processes we conclude that synaptic plasticity is reduced in the temporal cortex of 20-month-old rats. Remarkably, the induction of MAP1B in neuronal extensions was not impaired in the temporal cortex of older animals following intense neuronal activity. However, the aged rat brain responded more slowly to chemically-induced seizure although the levels of MAP1B induction are not decreased as compared to the levels expressed by 3-month-old rats.

Journal Article↗
PubMed2006

Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus.

DNA (cytosine-5) methylation represents one of the most widely used mechanisms of enduring cellular memory. Stable patterns of DNA methylation are established during development, resulting in creation of persisting cellular phenotypes. There is growing evidence that the nervous system has co-opted a number of cellular mechanisms used during development to subserve the formation of long term memory. In this study, we examined the role DNA (cytosine-5) methyltransferase (DNMT) activity might play in regulating the induction of synaptic plasticity. We found that the DNA within promoters for reelin and brain-derived neurotrophic factor, genes implicated in the induction of synaptic plasticity in the adult hippocampus, exhibited rapid and dramatic changes in cytosine methylation when DNMT activity was inhibited. Moreover, zebularine and 5-aza-2-deoxycytidine, inhibitors of DNMT activity, blocked the induction of long term potentiation at Schaffer collateral synapses. Activation of protein kinase C in the hippocampus decreased reelin promoter methylation and increased DNMT3A gene expression. Interestingly, DNMT activity is required for protein kinase C-induced increases in histone H3 acetylation. Considered together, these results suggest that DNMT activity is dynamically regulated in the adult nervous system and that DNMT may play a role in regulating the induction of synaptic plasticity in the mature CNS.

Animals↗
PubMed2002

Glutamate uptake in synaptic plasticity: from mollusc to mammal.

A great deal of research has been directed toward understanding the cellular mechanisms underlying synaptic plasticity and memory formation. To this point, most research has focused on the more "active" components of synaptic transmission: presynaptic transmitter release and postsynaptic transmitter receptors. Little work has been done characterizing the role neurotransmitter transporters might play during changes in synaptic efficacy. We review several new experiments that demonstrate glutamate transporters are regulated during changes in the efficacy of glutamatergic synapses. This regulation occurred during long-term facilitation of the sensorimotor synapse of Aplysia and long-term potentiation of the Schaffer-collateral synapse of the rat. We propose that glutamate transporters are "co-regulated" with other molecules/processes involved in synaptic plasticity, and that this process is phylogenetically conserved. These new findings indicate that glutamate transporters most likely play a more active role in neurotransmission than previously believed.

Amino Acid Transport System X-AG↗
PubMed2006

The in vivo synaptic plasticity mechanism of EGb 761-induced enhancement of spatial learning and memory in aged rats.

It has not been uniform to date that the Ginkgo biloba extracts enhance cognitive function in aged animals, and the mechanisms of action remain difficult to elucidate. In this study, the Morris water maze task and electrophysiological methods were used to study the effects of repeated daily administration of EGb 761, a standardized extract from G. biloba leaves, on hippocampal-dependent spatial learning and memory and synaptic plasticity of aged rats. The adult subjects perform the Morris water maze task better than aged rats, as a cellular mechanism, the hippocampal long-term potentiation (LTP) elicited from adult animals is robust (139.29+/-2.7%). In addition, the spatial learning and memory of aged rats that had been fed on an EGb 761-supplemented diet (60 mg kg(-1)) for 30 days were significantly better than those of control aged rats. The magnitude of LTP (116.63+/-3.6%) recorded in vivo from the hippocampus CA1 area of aged rats was significantly enhanced by EGb 761 (60 mg kg(-1)). In conclusion, the spatial learning and memory of aged rats is worse than that of young subjects, and EGb 761, acting as a 'cognitive enhancer', has benefit on synaptic plasticity and cognition in aged rats. The present data further confirmed that enhancement of synaptic plasticity of the hippocampus might ameliorate the deficit in spatial learning and memory in aged rats.

Aging↗
PubMed2003

GluR2 protein-protein interactions and the regulation of AMPA receptors during synaptic plasticity.

AMPA-type glutamate receptors mediate most fast excitatory synaptic transmissions in the mammalian brain. They are critically involved in the expression of long-term potentiation and long-term depression, forms of synaptic plasticity that are thought to underlie learning and memory. A number of synaptic proteins have been identified that interact with the intracellular C-termini of AMPA receptor subunits. Here, we review recent studies and present new experimental data on the roles of these interacting proteins in regulating the AMPA receptor function during basal synaptic transmission and plasticity.

Animals↗
PubMed2005

Role of the glycine site of the N-methyl-D-aspartate receptor in synaptic plasticity induced by pairing.

In the hippocampal CA1 region of the rat, activity-dependent plasticity requires substantial postsynaptic depolarization and activation of the N-methyl-D-aspartate glutamate receptor subtype (NMDAR). Exogenous and endogenous compounds selectively modulate NMDAR function by acting at the glycine coagonist site. Here we investigate the modulatory role of the glycine site in the induction of bidirectional synaptic plasticity. Plasticity was induced by pairing low-frequency afferent pulses with different levels of postsynaptic depolarization in the absence and presence of glycine site compounds. We found strong dependence of glycine site agonist modulation on membrane voltage during induction. Thus, D-serine and glycine were more effective in enhancing long-term potentiation (LTP) during pairing of small depolarization (-60 or -50 mV) with subthreshold EPSCs than during pairing of stronger depolarization (-40 mV) with suprathreshold synaptic responses. The glycine site role in bidirectional synaptic plasticity was studied with the selective antagonist 7-chlorokynurenic acid. Blockade of the glycine site during the pairing reversed the direction of plasticity from LTP towards long-term depression. The magnitude of depression was dependent on antagonist concentration and the level of depolarization during the pairing. Thus, these experiments demonstrate the role of the glycine site in the induction of bidirectional synaptic plasticity.

Afferent Pathways↗
PubMed2002

Synaptic plasticity, metaplasticity and BCM theory.

In many regions of the brain, the activity-dependent changes in synaptic strength depend on the frequency and timing of presynaptic stimulation and postsynaptic activity (synaptic plasticity), as well as the history of activity at those synapses (metaplasticity). The Bienenstock, Cooper and Munro (BCM) theory made several assumptions about how synapses modify and these have helped to guide various neurobiological and neurocomputational experiments. There does appear to be a good correspondence of the synaptic plasticity and metaplasticity experimental data with the BCM model. (Fig. 1, Ref. 57.).

Action Potentials↗
PubMed2000

Involvement of neurogranin in the modulation of calcium/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: a study with knockout mice.

Neurogranin/RC3 is a neural-specific Ca(2+)-sensitive calmodulin (CaM)-binding protein whose CaM-binding affinity is modulated by phosphorylation and oxidation. Here we show that deletion of the Ng gene in mice did not result in obvious developmental or neuroanatomical abnormalities but caused an impairment of spatial learning and changes in hippocampal short- and long-term plasticity (paired-pulse depression, synaptic fatigue, long-term potentiation induction). These deficits were accompanied by a decreased basal level of the activated Ca(2+)/CaM-dependent kinase II (CaMKII) ( approximately 60% of wild type). Furthermore, hippocampal slices of the mutant mice displayed a reduced ability to generate activated CaMKII after stimulation of protein phosphorylation and oxidation by treatments with okadaic acid and sodium nitroprusside, respectively. These results indicate a central role of Ng in the regulation of CaMKII activity with decisive influences on synaptic plasticity and spatial learning.

Animals↗
PubMed2006

[Experimental study on effects of electro-acupuncture in improving synaptic plasticity in focal cerebral ischemia rats].

OBJECTIVE: To explore the mechanisms of electro-acupuncture (EA) in improving synaptic plasticity after cerebral ischemic injury. METHODS: Focal cerebral ischemia (FCI) model was established by middle cerebral artery occlusion (MCAO) with heat-coagulation method. The changing rules of synaptic ultrastructure, synaptophysin (P38), growth-associated protein-43 (GAP-43), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the ischemic cortex 2 and 5 weeks after FCI and the effects of EA on them were observed. RESULTS: Expression of numerical density (Nv), surface density (Sv), volume density (Vv), post synaptic density (PSD) and P38 in the ischemic cortex significantly decreased after MCAO (P<0.01). Among them, Nv and Sv were raised at the 5th week in FCI rats either treated or untreated with EA (P<0.01), but the increment of Sv was higher in those of the treated rats (P<0.01); PSD in the EA treated rats also showed a significant increase at the 5th week, which was significant higher than that in those untreated; EA showed insignificant influence on Vv and synaptic interfacial curvature; P38 lowered continuously after 2 weeks, but at the 5th week, it was higher in EA treated rats than that in untreated rats (P<0.01), while at the 2nd week, the levels in treated and untreated rats were equal. GAP-43 rose in the 2nd week after modeling, with no difference between EA treated and untreated animals, at the 5th week, it was lowered in untreated rats to near that in sham-operated rats, but maintained at higher level in EA treated rats; NGF and BDNF positive cells significantly increased after modeling (P<0.01), and showed a descending trend with the time going (P<0.01) both in rats treated or untreated with EA. CONCLUSION: EA can protect synaptic ultrastructure, promote the expression of P38, GAP-43, NGF and BDNF in the ischemic cerebral cortex, and thus improve synaptic plasticity in cerebral ischemic rats.

Acupuncture Therapy↗
PubMed1996

Protein kinase and phosphatase activity regulate the form of synaptic plasticity expressed.

Long-term potentiation (LTP) and long-term depression (LTD) are calcium-dependent forms of synaptic plasticity observed in area CA1 of the hippocampus. Low-frequency tetani (1-5 Hz) activates protein phosphatases to induce LTD, whereas high-frequency tetani (> 25 Hz) activates protein kinases to induce LTP. A tetanus at an intermediate frequency (10 Hz), however, does not result in a change in synaptic efficacy [Dudek and Bear, (1992), Proc. Natl. Acad. Sci. USA, 89:4363-4367]. We hypothesized that the 10-Hz tetanus results in no long-term change in synaptic efficacy due to a balance of the activity of protein phosphatases and protein kinases. We manipulated protein kinase/phosphatase activity at a 10-Hz tetanus to test this hypothesis. A 10-Hz tetanus under normal conditions results in a transient depression which returns to baseline in 25 min. However, inhibiting kinase activity with the protein kinase inhibitor H-7, or decreasing extracellular calcium concentration, results in the 10-Hz tetanus, inducing LTD. Conversely, inhibiting phosphatase activity with the protein phosphatase inhibitor tautomycin, or increasing extracellular calcium concentration, results in the 10-Hz tetanus, inducing LTP. These results suggest that the relative balance of protein kinase and phosphatase activity (and/or the calcium levels activating them) determines the expression of specific forms of synaptic plasticity, and that these forms lie on a continuum.

Animals↗
PubMed2003

Long-lasting effects of neonatal dexamethasone treatment on spatial learning and hippocampal synaptic plasticity: involvement of the NMDA receptor complex.

The effects of neonatal dexamethasone (DEX) treatment on spatial learning and hippocampal synaptic plasticity were investigated in adult rats. Spatial learning in reference and working memory versions of the Morris maze was impaired in DEX-treated rats. In hippocampal slices of DEX rats, long-term depression was facilitated and potentiation was impaired. Paired-pulse facilitation was normal, suggesting a postsynaptic defect as cause of the learning and plasticity deficits. Western blot analysis of hippocampal postsynaptic densities (PSD) revealed a reduction in NR2B subunit protein, whereas the abundance of the other major N-methyl-D-aspartate (NMDA) receptor subunits (NR1, NR2A), AMPA receptor subunits (GluR2/3), scaffolding proteins, and Ca2+/calmodulin-dependent protein kinase II (alphaCaMKII) were unaltered. This selective reduction in NR2B likely resulted from altered receptor assembly rather than subunit expression, because the abundance of NR2B in the homogenate and crude synaptosomal fractions was unaltered. In addition, the activity of alphaCaMKII, an NMDA receptor complex associated protein kinase, was increased in PSD of DEX rats. The results indicate that neonatal treatment with DEX causes alterations in composition and function of the hippocampal NMDA receptor complex that persist into adulthood. These alterations likely explain the deficits in hippocampal synaptic plasticity and spatial learning induced by neonatal DEX treatment.

Animals↗
PubMed2005

Vulnerability of synaptic plasticity in the complexin II knockout mouse to maternal deprivation stress.

The alterations in brain function and structure seen in schizophrenia are mediated by genetics as well as vulnerability due to environmental factors. Postmortem studies in schizophrenic patients have shown that expression of complexin II, which is involved in neurotransmitter release at central nervous system synapses, is decreased in the brain. We examined the physiological characteristics of complexin II gene-deficient mice subjected to maternal deprivation stress to determine whether psychological stress during the early stage of life affected the development of brain function. We compared the electrophysiological properties of CA1 hippocampal pyramidal neurons and spatial memory in the Morris water maze test in the wild-type mouse and the homozygous mutant. In the non-stressed mouse, no significant differences in transsynaptic responses and synaptic plasticity or spatial memory were seen, suggesting that complexin II does not play a critical role in transmitter release or synaptic plasticity under these conditions. In contrast, under conditions of maternal deprivation stress, the knockout mouse showed a significant decrease in post-tetanic potentiation and LTP induction and a significant impairment in Morris water Maze test compared to the wild-type mouse, suggesting that complexin II plays a significant role in neurotransmitter release and synaptic plasticity under this pathological condition. Taken together, these results show that mice lacking complexin II are vulnerable to maternal deprivation stress, which raises the possibility that the complexin II gene may be a factor in the onset of schizophrenia.

Adaptor Proteins, Vesicular Transport↗