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Results for “synaptic plasticity”

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At least 217 records · Page 12Linked to original sources
PubMed2001

Extracellular signal-regulated kinase, synaptic plasticity, and memory.

The mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK), has been studied extensively in recent years for its involvement in synaptic plasticity and memory function. Activation of ERK is coupled to stimulation of cell-surface proteins via several different upstream signaling pathways, and contributes to the regulation of diverse cellular processes, ranging from cell excitability to gene expression. We herein review evidence for ERK's role in different forms of synaptic plasticity and different types of learning paradigms, drawing on examples from different systems in molluscs as well as the mammalian brain. The picture that emerges is that ERK activation in response to conditions that give rise to synaptic and behavioral modification contributes to that modification in a multitude of functionally distinct ways. The functional diversity is likely to be achieved by the operation of multiple, parallel ERK cascades that differ with respect to the subcellular compartments in which ERK exerts its effects and the temporal windows during which the effects are manifested. We conclude that our understanding of the mechanisms by which ERK contributes to synaptic plasticity and memory has much to gain by further study of the signaling events up- and downstream of ERK activation and the spatiotemporal characteristics of ERK activation in association with activity-dependent synaptic modification and information processing.

Amygdala↗
PubMed2005

Modulation of synaptic plasticity by physiological activation of M1 muscarinic acetylcholine receptors in the mouse hippocampus.

The muscarinic acetylcholine receptor (mAChR) has been considered one of the neurotransmitter receptors regulating hippocampal synaptic plasticity, which likely plays a critical role in learning and memory. In previous studies, however, muscarinic agonists were used at relatively high concentrations, and the subtype selectivity of muscarinic antagonists was not satisfactory. Thus, it remains to be answered whether physiological levels of ACh are involved in the regulation of synaptic plasticity and which mAChR subtypes are responsible for such effects. We found in this study that a low concentration (50 nM) of carbachol enhanced long-term potentiation (LTP) of excitatory synaptic transmission in mouse hippocampal slices. Notably, this enhancing effect was abolished in M1 mAChR knock-out (KO) but not in M3 mAChR KO mice, although LTP itself was intact in both mutant mice. Furthermore, we found that repetitive stimulation in the stratum oriens, which presumably triggered the release of endogenous ACh from cholinergic terminals, could enhance LTP in wild-type mice but not in M1 mAChR KO mice. These results suggest that physiologically released ACh from cholinergic fibers modulates hippocampal synaptic plasticity through the postsynaptic M1 mAChR activation.

Acetylcholine↗
PubMed1998

Synaptic plasticity: going through phases with LTP.

Early and late expressing components of synaptic plasticity may underlie the temporal phases of behavioral memory. New studies argue that a balance between kinase and phosphatase activity regulates the transition between different phases of synaptic plasticity and memory.

Animals↗
PubMed2006

Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories.

Arc/Arg3.1 is robustly induced by plasticity-producing stimulation and specifically targeted to stimulated synaptic areas. To investigate the role of Arc/Arg3.1 in synaptic plasticity and learning and memory, we generated Arc/Arg3.1 knockout mice. These animals fail to form long-lasting memories for implicit and explicit learning tasks, despite intact short-term memory. Moreover, they exhibit a biphasic alteration of hippocampal long-term potentiation in the dentate gyrus and area CA1 with an enhanced early and absent late phase. In addition, long-term depression is significantly impaired. Together, these results demonstrate a critical role for Arc/Arg3.1 in the consolidation of enduring synaptic plasticity and memory storage.

Analysis of Variance↗
PubMed2003

Transmitter metabolism as a mechanism of synaptic plasticity: a modeling study.

The nervous system adapts to experience by changes in synaptic strength. The mechanisms of synaptic plasticity include changes in the probability of transmitter release and in postsynaptic responsiveness. Experimental and neuropharmacological evidence points toward a third variable in synaptic efficacy: changes in presynaptic transmitter concentration. Several groups, including our own, have reported changes in the amplitude and frequency of postsynaptic (miniature) events indicating that alterations in transmitter content cause alterations in vesicular transmitter content and vesicle dynamics. It is, however, not a priori clear how transmitter metabolism will affect vesicular transmitter content and how this in turn will affect pre- and postsynaptic functions. We therefore have constructed a model of the presynaptic terminal incorporating vesicular transmitter loading and the presynaptic vesicle cycle. We hypothesize that the experimentally observed synaptic plasticity after changes in transmitter metabolism puts predictable restrictions on vesicle loading, cytoplasmic-vesicular transmitter concentration gradient, and on vesicular cycling or release. The results of our model depend on the specific mechanism linking presynaptic transmitter concentration to vesicular dynamics, that is, alteration of vesicle maturation or alteration of release. It also makes a difference whether differentially filled vesicles are detected and differentially processed within the terminal or whether vesicle filling acts back onto the terminal by presynaptic autoreceptors. Therefore, the model allows one to decide, at a given synapse, how transmitter metabolism is linked to presynaptic function and efficacy.

Animals↗
PubMedDate not supplied

Potential for multiple mechanisms, phenomena and algorithms for synaptic plasticity at single synapses.

Recent experimental evidence indicates that in the neocortex, the manner in which each synapse releases neurotransmitter in response to trains of presynaptic action potentials is potentially unique. These unique transmission characteristics arise because of a large heterogeneity in various synaptic properties that determine frequency dependence of transmission such as those governing the rates of synaptic depression and facilitation. A theoretical analysis was therefore undertaken to explore the phenomenologies of changes in the values of these synaptic parameters. The results illustrate how the change in any one of several synaptic parameters produces a distinctive effect on synaptic transmission and how these distinctive effects can point to the most likely biophysical mechanisms. These results could therefore be useful in studies of synaptic plasticity in order to obtain a full characterization of the phenomenologies of synaptic modifications and to isolate potential biophysical mechanisms. Based on this theoretical analysis and experimental data, it is proposed that there exists multiple mechanisms, phenomena and algorithms for synaptic plasticity at single synapses. Finally, it is shown that the impact of changing the values of synaptic parameters depends on the values of the other parameters. This may indicate that the various mechanisms, phenomena and algorithms are interlinked in a 'synaptic plasticity code'.

Algorithms↗
PubMed2002

Selective modification of short-term hippocampal synaptic plasticity and impaired memory extinction in mice with a congenitally reduced hippocampal commissure.

The hippocampus is critical for forming new long-term memories, but the contributions of the hippocampal commissure (HC) to memory function and hippocampal synaptic plasticity are unclear. To shed light on this issue, we characterized behavioral memory and hippocampal synaptic plasticity in two inbred mouse strains. BALB/cWah1 mice display a range of corpus callosal defects and an intact HC, whereas 9XCA/Wah mice exhibit a complete absence of corpus callosum and a greatly reduced HC. No differences between strains were found in long-term potentiation (LTP) within two synaptic pathways in hippocampal slices. However, paired-pulse facilitation was deficient in area CA1 of slices from 9XCA/Wah, and it was rescued by decreasing extracellular [Ca2+], suggesting that presynaptic calcium dynamics may be altered in this strain. In addition, contextual fear extinction was impaired in 9XCA/Wah mice, but performance on cued fear extinction and on 24 hr memory tests for cued and contextual fear conditioning were not significantly different between strains. Thus, an intact HC is critical for normal extinction of contextual fear. Intact interhemispheric connectivity is not required for acquisition or expression of cued and contextual fear conditioning. LTP was normal in slices from mice that lacked an intact HC, and this was correlated with normal performance on fear conditioning tests. In contrast, impaired short-term synaptic plasticity was correlated with defective contextual memory extinction in mice lacking an intact HC. Thus, the HC in mice is vital for particular aspects of memory function and for short-term synaptic modification in specific hippocampal circuits.

Agenesis of Corpus Callosum↗
PubMed2000

The role of acetylcholine in cortical synaptic plasticity.

This review examines the role of acetylcholine in synaptic plasticity in archi-, paleo- and neocortex. Studies using microiontophoretic application of acetylcholine in vivo and in vitro and electrical stimulation of the basal forebrain have demonstrated that ACh can produce long-lasting increases in neural responsiveness. This evidence comes mainly from models of heterosynaptic facilitation in which acetylcholine produces a strengthening of a second, noncholinergic synaptic input onto the same neuron. The argument that the basal forebrain cholinergic system is essential in some models of plasticity is supported by studies that have selectively lesioned the cholinergic basal forebrain. This review will examine the mechanisms whereby acetylcholine might induce synaptic plasticity. It will also consider the neural circuitry implicated in these studies, namely the pathways that are susceptible to cholinergic plasticity and the neural regulation of the cholinergic system.

Acetylcholine↗
PubMed2006

A new synaptic plasticity rule for networks of spiking neurons.

In this paper, we describe a new Synaptic Plasticity Activity Rule (SAPR) developed for use in networks of spiking neurons. Such networks can be used for simulations of physiological experiments as well as for other computations like image analysis. Most synaptic plasticity rules use artificially defined functions to modify synaptic connection strengths. In contrast, our rule makes use of the existing postsynaptic potential values to compute the value of adjustment. The network of spiking neurons we consider consists of excitatory and inhibitory neurons. Each neuron is implemented as an integrate-and-fire model that accurately mimics the behavior of biological neurons. To test performance of our new plasticity rule we designed a model of a biologically-inspired signal processing system, and used it for object detection in eye images of diabetic retinopathy patients, and lung images of cystic fibrosis patients. The results show that the network detects the edges of objects within an image, essentially segmenting it. Our ultimate goal, however, is not the development of an image segmentation tool that would be more efficient than nonbiological algorithms, but developing a physiologically correct neural network model that could be applied to a wide range of neurological experiments. We decided to validate the SAPR by using it in a network of spiking neurons for image segmentation because it is easy to visually assess the results. An important thing is that image segmentation is done in an entirely unsupervised way.

Algorithms↗
PubMed1993

NMDA-receptor-dependent synaptic plasticity: multiple forms and mechanisms.

Long-term potentiation in the CA1 region of the hippocampus is the most extensively studied model of activity-dependent synaptic plasticity in the mammalian brain. Its induction normally involves activation of postsynaptic N-methyl-D-aspartate (NMDA) receptors, which are thought to control the occurrence of long-term potentiation at individual synapses. Recent work in the hippocampus indicates that NMDA receptor activation does not necessarily lead to induction of long-term potentiation but instead may elicit a repertoire of distinct forms of synaptic plasticity including short-term potentiation or long-term depression. Furthermore, mechanisms exist such that the induction of long-term potentiation can be inhibited by modest activation of NMDA receptors. Experimental results are beginning to clarify the mechanistic relationships between these different phenomena, although much remains unknown. Whatever their underlying mechanisms, these additional forms of NMDA-receptor-dependent synaptic plasticity confer increased flexibility to neural circuits involved in information processing and storage.

Animals↗
PubMed2003

Synaptic plasticity in thalamic nuclei enhanced by motor skill training in rat with transient middle cerebral artery occlusion.

The goal of this study was to determine if synaptic plasticity in the thalamus of rats subjected to stroke could be altered by motor training. Transient occlusion of right middle cerebral artery in adult female Sprague-Dawley rats (n = 35) was induced with an intraluminal filament followed by three training conditions, 1. motor skill training on Rota-rod requiring balance and coordination skills, 2. simple exercise on treadmill, and 3. nontrained controls. Synaptic plasticity in brain was evaluated by synapotophysin immunocytochemistry at 14 or 28 days after training procedures. Infarct volume was determined in Nissl stained sections. Both at 14 and 28 days after Rota-rod training, intense synaptophysin immunoreactivity was present in the right but not the left mediodorsal and ventromedial nuclei of thalamus of ischemic rats. In treadmill-trained animals, however, similarly intense synaptic plasticity in these two thalamic nuclei was seen only at 28 days. Immunostaining was found also in other brain regions adjacent to or remote from infarct site. The data suggest that motor training, particularly motor skill training involving balance and coordination, facilitates a uniquely lateralized synaptogenesis in the thalamus.

Animals↗
PubMed2001

Chronic imipramine treatment partially reverses the long-term changes of hippocampal synaptic plasticity in socially stressed rats.

In the present study, we investigated whether synaptic plasticity changes in the hippocampus of depressive-like socially stressed rats could be reversed by chronic antidepressant treatment. To that end, rats were either defeated and subsequently individually housed or subjected to control treatment followed by social housing. After a period of at least 3 months, rats were either treated chronically with imipramine (20 mg/kg per day, per os for at least 3 months) or the solvent solution (i.e. water). Then, long-term potentiation and depression were measured in the CA1 region of the hippocampus in vitro. Chronic imipramine treatment partially restored the attenuated induction of long-term potentiation and suppressed the facilitation of long-term depression-induction in socially stressed rats. The altered synaptic plasticity after social stress is discussed in relation to cognitive deficits and hippocampal changes that are observed in depressive patients.

Animals↗
PubMed2006

Altered signaling pathways underlying abnormal hippocampal synaptic plasticity in the Ts65Dn mouse model of Down syndrome.

The Ts65Dn mouse model of Down syndrome (DS) has an extra segment of chromosome (Chr.) 16 exhibits abnormal behavior, synaptic plasticity and altered function of several signaling molecules. We have further investigated signaling pathways that may be responsible for the impaired hippocampal plasticity in the Ts65Dn mouse. Here we report that calcium/calmodulin-dependent protein kinase II (CaMKII), phosphatidylinositol 3-kinase (PI3K)/Akt, extracellular signal-regulated kinase (ERK), protein kinase A (PKA) and protein kinase C (PKC), all of which have been shown to be involved in synaptic plasticity, are altered in the Ts65Dn hippocampus. We found that the phosphorylation of CaMKII and protein kinase Akt was increased, whereas ERK was decreased. Activities of PKA and PKC were decreased. Furthermore, abnormal PKC activity and an absence of the increase in Akt phosphorylation were demonstrated in the Ts65Dn hippocampus after high-frequency stimulation that induces long-term potentiation. Our findings suggest that abnormal synaptic plasticity in the Ts65Dn hippocampus is the result of compensatory alterations involving the glutamate receptor subunit GluR1 in either one or more of these signaling cascades caused by the expression of genes located on the extra segment of Chr. 16.

Animals↗
PubMed2006

"The seven sins" of the Hebbian synapse: can the hypothesis of synaptic plasticity explain long-term memory consolidation?

Memorizing new facts and events means that entering information produces specific physical changes within the brain. According to the commonly accepted view, traces of memory are stored through the structural modifications of synaptic connections, which result in changes of synaptic efficiency and, therefore, in formations of new patterns of neural activity (the hypothesis of synaptic plasticity). Most of the current knowledge on learning and initial stages of memory consolidation ("synaptic consolidation") is based on this hypothesis. However, the hypothesis of synaptic plasticity faces a number of conceptual and experimental difficulties when it deals with potentially permanent consolidation of declarative memory ("system consolidation"). These difficulties are rooted in the major intrinsic self-contradiction of the hypothesis: stable declarative memory is unlikely to be based on such a non-stable foundation as synaptic plasticity. Memory that can last throughout an entire lifespan should be "etched in stone." The only "stone-like" molecules within living cells are DNA molecules. Therefore, I advocate an alternative, genomic hypothesis of memory, which suggests that acquired information is persistently stored within individual neurons through modifications of DNA, and that these modifications serve as the carriers of elementary memory traces.

Animals↗
PubMed1985

Protein kinase C activation leading to protein F1 phosphorylation may regulate synaptic plasticity by presynaptic terminal growth.

It has recently been proposed by the author that protein kinase C regulates the expression of synaptic plasticity. In the present review it is suggested that this regulation involves a growth of presynaptic terminals. This proposal was based on the discovery that one of the substrates of protein kinase C, protein F1 (molecular mass = 47 kDa, pI = 4.5) is increased in its phosphorylation 5 min, 1 hr, and 3 days following long-term potentiation (LTP) in the intact hippocampal formation. No other phosphoprotein studied was altered by LTP. The amplitude or persistence of synaptic plasticity was directly related to the extent of protein F1 phosphorylation. As a critical control, it was shown that protein F1 was unaltered following synaptic activation that did not alter synaptic strength. Protein F1 in the hippocampus was also altered in its phosphorylation after an experience involving memory of a spatial environment. Phosphorylation F1 may thus participate in both neurophysiological and behavioral events that evoke plasticity. The identification of the F1 substrate has recently been sought. The physical characteristics of protein F1 (mol wt., isoelectric point) indicate that it is the same as the B-50 protein and the growth protein, GAP-43. Protein F1 is then a brain-specific, synaptically enriched phosphoprotein. Recent evidence indicates that protein F1 is present in high concentration in growth cones of late embryonic rat brain in which postsynaptic specializations are not detected, suggesting a presynaptic locus. With respect to the identity of the F1 kinase, we have shown that protein F1, like B-50, is a substrate for protein kinase C, a Ca2+/phospholipid-dependent kinase. Activation of this enzyme by tumor-promoting phorbol esters can trigger cell growth and neurite extension. Recent evidence indicates a presynaptic localization of the enzyme. On the basis of the colocalization of enzyme and substrate in the presynaptic terminal it is proposed that protein kinase C control of the phosphorylation state of protein F1 may regulate the expression of synaptic plasticity via presynaptic terminal growth.

Animals↗
PubMed2001

Effects of T-588, a cognitive enhancer compound, on synaptic plasticity in the dentate gyrus of freely moving rats.

(1R)-1-benzo [b] thiophen-5-yl-2-[2-(diethylamino) ethoxy] ethan-1-ol hydrochloride (T-588) is a compound for the treatment of neurodegenerative disorders, including Alzheimer's disease and cerebrovascular diseases. T-588 reportedly alleviates learning and memory deficits in animal models of dementia. In the present study, we investigated the effects of T-588 on the induction and decay of long-term potentiation (LTP) and on the responses to paired-pulse (pp) stimulation in freely moving rats. Perforant path-evoked field potentials were recorded in the dentate gyrus by chronically implanted electrodes. LTP was induced by high-frequency stimulation 30 min after oral administration of T-588 (0.3 or 3 mg/kg). T-588 significantly augmented the increase in population spike amplitude and field excitatory postsynaptic potential slope after LTP induction. T-588 also prolonged the decay of augmented population spike amplitude, but had no significant effect on the response to pp stimulation. These results suggest that T-588 facilitates long-term synaptic plasticity, but not short-term synaptic plasticity in the dentate gyrus of freely moving rats. The effect of T-588 on long-term synaptic plasticity may contribute to the alleviation of learning and memory dysfunction seen in animal models.

Animals↗
PubMed1995

Properties and mechanisms of long-term synaptic plasticity in the mammalian brain: relationships to learning and memory.

Long-term potentiation (LTP) in the hippocampus and long-term depression (LTD) in the cerebellum are two forms of long-lasting synaptic plasticity that currently serve as our primary experimental models of learning and memory formation in mammals. In recent years, there have been considerable advances in our understanding of the cellular and molecular mechanisms of these and other forms of synaptic plasticity. This article presents an overview of these developments, considers the relationship of long-term synaptic plasticity mechanisms to learning and memory in view of these developments, and suggests future directions for research in this rapidly growing area of neuroscience.

Animals↗
PubMed2003

The effect of brain-derived neurotrophic factor on neuritogenesis and synaptic plasticity in Aplysia neurons and the hippocampal cell line HiB5.

Brain-derived neurotrophic factor (BDNF) plays a key role in the differentiation and neuritogenesis of developing neurons, and in the synaptic plasticity of mature neurons, in the mammalian nervous system. BDNF binds to the receptor tyrosine kinase TrkB and transmits neurotrophic signals by activating neuron-specific tyrosine phosphorylation pathways. However, the neurotrophic function of BDNF in Aplysia neurons is poorly understood. We examined the specific effect of BDNF on neurite outgrowth and synaptic plasticity in cultured Aplysia neurons and a multipotent rat hippocampal stem cell line (HiB5). Our study indicates that mammalian BDNF has no significant effect on the neuritogenesis, neurotransmitter release, excitability, and synaptic plasticity of cultured Aplysia neurons in our experimental conditions. In contrast, BDNF in combination with platelet-derived growth factor (PDGF) increases the length of the neurites and the number of spine-like structures in cells of HiB5.

Animals↗