Search PubMed⌕ Search

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.

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

At least 397 records · Page 22Linked to original sources
PubMed2004

The 5-hydroxytryptamine4 receptor exhibits frequency-dependent properties in synaptic plasticity and behavioural metaplasticity in the hippocampal CA1 region in vivo.

Long-term plasticity, in the forms of long-term depression (LTD) and long-term potentiation (LTP), of synaptic transmission are thought to underlie memory. Biogenic amino acids modulate the expression of LTD and LTP. The serotonergic 5-hydroxytryptamine4 (5-HT4) receptor has been shown to influence learning and memory. However, little is known about the role of this receptor in synaptic plasticity. Here we show that although induction of LTP is unaffected by either pharmacological activation or inhibition of 5-HT4, application of the 5-HT4 receptor agonist, RS67333, completely blocks learning-induced depotentiation of LTP in the hippocampal CA1 region of freely moving rats, suggesting a role for 5-HT4 receptors in behavioural metaplasticity. In addition, the 5-HT4 antagonist RS39604 enhances the intermediate phase of LTD and converts short-term depression into persistent LTD (>24 h), suggesting a significant role for 5-HT4 receptors in the expression of LTD in CA1. Stimulation at 10 Hz causes transient synaptic depression. However, 5-HT4 antagonist application prior to 10 Hz stimulation leads to LTD, whereas agonist application leads to LTP expression. 5-HT4 receptors thus shift the frequency-response relationship for induction of plasticity. Together, these findings suggest a key role for 5-HT4 receptors in the regulation of synaptic plasticity and the determination of the particular properties of stored synaptic information.

Aniline Compounds↗
PubMed2004

Molecular determinants mediating effects of acute stress on hippocampus-dependent synaptic plasticity and learning.

The understanding of the molecular events underlying the neuroendocrine and behavioral sequelae of the response to stress has advanced rapidly over recent years. The hippocampus is a target of stress hormones, and we are beginning to dissect the molecular players in the modulation of synaptic plasticity and learning and memory involving this region of the brain. Given the wealth of data obtained from electrophysiological and behavioral experiments and in view of the importance to use identical experimental protocols in order to correlate the results obtained under both experimental conditions, this review focuses primarily on those contributions, which combine both approaches. From these studies it is evident that a single stressful event elicits responses in the hippocampus with different time-spans ranging from rapid changes in glutamatergic neurotransmission (i.e., N-methyl-d-aspartate receptor signaling), activation of second messenger cascades by corticotropin-releasing factor to long-lasting transcriptional changes of acetylcholinesterase. The relative contribution of these molecular targets to the stress response, the relation to hippocampal synaptic plasticity and memory formation, and the possible interaction of the underlying processes are discussed.

Acute Disease↗
PubMed2004

Reactive oxygen species and synaptic plasticity in the aging hippocampus.

Aging is associated with a general decline in physiological functions including cognitive functions. Given that the hippocampus is known to be critical for certain forms of learning and memory, it is not surprising that a number of neuronal processes in this brain area appear to be particularly vulnerable to the aging process. Long-term potentiation (LTP), a form of synaptic plasticity that has been proposed as a biological substrate for learning and memory, has been used to examine age-related changes in hippocampal synaptic plasticity. A current hypothesis states that oxidative stress contributes to age-related impairment in learning and memory. This is supported by a correlation between age, memory impairment, and the accumulation of oxidative damage to cellular macromolecules. However, it also has been demonstrated that ROS are necessary components of signal transduction cascades during normal physiological processes. This review discusses the evidence supporting the dual role of reactive oxygen species (ROS) as cellular messenger molecules in normal LTP, as well their role as damaging toxic molecules in the age-related impairment of LTP. In addition, we will discuss parallel analyses of LTP and behavioral tests in mice that overexpress antioxidant enzymes and how the role of antioxidant enzymes and ROS in modulating these processes may vary over the lifespan of an animal.

Aging↗
PubMed2005

Synaptic plasticity in the dy2J mouse model of laminin alpha2-deficient congenital muscular dystrophy.

Laminin alpha2-deficient congenital muscular dystrophy is a debilitating disease affecting both muscle and neural tissue as a result of mutations in the LAMA2 gene. It presents at or soon after birth with muscle weakness and is further characterised by clinical central nervous system involvement. Laminin alpha2 is part of the extracellular matrix, linked to the cellular cystoskeleton via dystroglycan which is an integral part of the dystrophin-glycoprotein complex (DGC). We examined both short- and long-term synaptic plasticity in the C57BL6J/dy(2J) mouse, an animal model of laminin alpha2 deficient congenital muscular dystrophy. Using a cerebellar slice preparation, we show that the pre-synaptically mediated paired-pulse facilitation (PPF) was no different between dy(2J) and littermate controls. Approximately half (7/12) the dy(2J) Purkinje cells displayed a blunted LTD compared to littermate controls, and one third (4/12) of dy(2J) Purkinje cells displayed LTP. This study demonstrates that a defective laminin alpha2 causes a disruption in long-term synaptic plasticity at the Purkinje cell-parallel fibre synapse.

Animals↗
PubMed1999

Caspase and calpain substrates: roles in synaptic plasticity and cell death.

Neurons are an unusual type of cell in that they send processes (axons and dendrites) over great distances. This elaborate morphology, together with their excitability, places neurons at risk for multiple insults. Recent studies have demonstrated that apoptotic and excitotoxic mechanisms not only contribute to neuronal death, but also to synaptic dysfunction and a breakdown in neural circuitry (see Mattson and Duan [1999] J. Neurosci. Res. 58:152-166, this issue). Proteases of the caspase and calpain families have been implicated in neurodegenerative processes, as their activation can be triggered by calcium influx and oxidative stress. Caspases and calpains are cysteine proteases that require proteolytic cleavage for activation. The substrates cleaved by caspases include cytoskeletal and associated proteins, kinases, members of the Bcl-2 family of apoptosis-related proteins, presenilins and amyloid precursor protein, and DNA-modulating enzymes. Calpain substrates include cytoskeletal and associated proteins, kinases and phosphatases, membrane receptors and transporters, and steroid receptors. Many of the substrates of caspases and calpains are localized in pre- and/or postsynaptic compartments of neurons. Emerging data suggest that, in addition to their roles in neurodegenerative processes, caspases and calpains play important roles in modulating synaptic plasticity. The present article provides a review of the properties of the different caspases and calpains, their roles in cell death pathways, and the substrates upon which they act. Emerging data are considered that suggest key roles for these proteases in the regulation of synaptic plasticity.

Animals↗
PubMed2002

Synaptic plasticity and mood disorders.

Recent studies demonstrate that the molecular elements known to regulate neuronal plasticity in models of learning and memory are also involved in the actions of drugs used for the treatment of depression and bipolar disorder. This includes up-regulation of transcription factors, such as the cAMP response element binding protein and neurotrophic factors, such as brain derived neurotrophic factor. These findings raise the possibility that regulation of neural plasticity in specific neuronal circuits is integrally involved in the therapeutic intervention of mood disorders. Atypical antipsychotic drugs, including clozapine and olanzapine, are also effective for the treatment of bipolar disorder, and are used as add-on medication for unipolar depression. The possibility that these atypical antipsychotic drugs also influence the molecular determinants of synaptic plasticity that are involved in the response to drugs used for the treatment of mood disorders, is discussed.

Antidepressive Agents↗
PubMed2004

Orchestration of synaptic plasticity through AKAP signaling complexes.

Significant progress has been made toward understanding the mechanisms by which organisms learn from experiences and how those experiences are translated into memories. Advances in molecular, electrophysiological and genetic technologies have permitted great strides in identifying biochemical and structural changes that occur at synapses during processes that are thought to underlie learning and memory. Cellular events that generate the second messenger cyclic AMP (cAMP) and activate protein kinase A (PKA) have been linked to synaptic plasticity and long-term memory. In this review we will focus on the role of PKA in synaptic plasticity and discuss how the compartmentalization of PKA through its association with A-Kinase Anchoring Proteins (AKAPs) affect PKA function in this process.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Effects of endothelin-1 on hippocampal synaptic plasticity.

We examined the effects of puff application of endothelin (ET)-1 on the induction of long-term potentiation (LTP) and heterosynaptic long-term depression (LTD) in hippocampal CA1 slices. ET-1 applied 2 min prior to tetanus blocked the induction of LTP, but facilitated the induction of heterosynaptic LTD. These ET-1 effects on synaptic plasticity were dose-dependent, and not due to a generalized depression of baseline responses. ET-1 did not alter NMDA receptor-mediated responses. These data provide the first evidence that endothelin modulates activity-dependent synaptic plasticity, and the potency of these effects suggests that endogenous ET-1 may play an important role in regulating memory storage processes.

Animals↗
PubMedDate not supplied

[Mathematical model of development of long-term synaptic plasticity].

Proposed mathematical model is described the long-term synaptic plasticity creation as the postsynaptic process based on the number of membrane receptor increase. The transmitter as the "marker" of the receptor type synthesis and the protein kinase as the activator of this protein synthesis are proposed.

Models, Theoretical↗
PubMed2005

Impaired synaptic plasticity and learning in mice lacking beta-adducin, an actin-regulating protein.

The adducin family of proteins interacts with the actin cytoskeleton and the plasma membrane in a calcium- and cAMP-dependent manner. Thus, adducins may be involved in changes in cytoskeletal organization resulting from synaptic stimulation. beta-Adducin knock-out mice were examined in physiological and behavioral paradigms related to synaptic plasticity to elucidate the role the adducin family plays in processes underlying learning and memory. In situ hybridization for alpha- and beta-adducin demonstrates that these mRNAs are found throughout the brain, with high levels of expression in the hippocampus. Schaffer collateral-CA1 tetanic long-term potentiation decayed rapidly in acute hippocampal slices from beta-adducin knock-out mice, although baseline spine morphology and postsynaptic density were normal. Interestingly, the input-output relationship was significantly increased in hippocampal slices from beta-adducin knock-out mice. Furthermore, beta-adducin knock-out mice were impaired in performance of fear conditioning and the water maze paradigm. The current results indicate that beta-adducin may play an important role in the cellular mechanisms underlying activity-dependent synaptic plasticity associated with learning and memory.

Actins↗
PubMed1994

The cortical component of experience-dependent synaptic plasticity in the rat barrel cortex.

Rats were raised with altered tactile experience from P0 by removing all but one vibrissa (D1) from one side of the face (D1-spared animals). This procedure (univibrissa rearing) has previously been shown to cause neurons in cortical barrels surrounding D1 to develop greater than normal responses to D1 vibrissa stimulation and smaller than normal responses to principal vibrissa stimulation (Fox, 1992). In this study, it was found that the potentiated D1 responses could be attenuated by acute microlesions placed in the D1 barrel, while principal vibrissa responses were unchanged or even slightly elevated for the same cases. The ratio of the average D1 to principal vibrissa response was approximately proportional to the volume of tissue damaged in the D1 barrel. This result implies that the synaptic plasticity seen in cortex of D1-spared animals is due to synaptic changes that take place within the barrel cortex rather than to relay of changes occurring at a subcortical level. In addition, lesions aimed at the septum between D1 and an adjacent barrel almost completely abolished responses to D1 stimulation in that barrel, including short-latency responses (5-10 msec). Only neurons severed horizontally from D1 were affected. Neurons that maintained a connection with the D1 barrel via a bridge of septal tissue preserved their usual elevated levels of response to D1 stimulation and their aberrant short-latency responses. This result implies that pathways radiating out from the D1 barrel/column, and connecting neurons in the D1 barrel to cells in surrounding barrels, undergo synaptic plasticity induced by univibrissa rearing.

Animals↗
PubMed2005

Altered distribution of striatal activity-dependent synaptic plasticity in the 3-nitropropionic acid model of Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder characterized by involuntary choreiform movements, neuropsychiatric disturbances and cognitive decline. The hyperkinetic phenomenology has commonly been attributed to a disturbance of the basal ganglia function, mainly the neostriatum, but its pathophysiology mechanisms remain unclear. Activity-dependent long-term changes in synaptic efficacy, such as long-term potentiation (LTP) and long-term depression (LTD), are widely considered to be the cellular models for acquisition and storage of information in neuronal networks. Both LTP and LTD have been described at the corticostriatal pathway and they might be probably involved not only in physiological motor behavior processing but also in disease states affecting that pathway. Systemic injection of 3-nitropropionic acid (3-NP) induces excitotoxic striatal lesions and abnormal movements in rodents, resembling those seen in HD. We examined synaptic plasticity in dorsolateral striatum slices prepared from both control and 3-NP-treated rats by recording extracellular field potentials. Our results reinforce the idea that both forms of activity-dependent synaptic plasticity can be recorded at the dorsolateral region of striatum by the same stimulating protocol in control rats and suggest that 3-NP-induced striatal lesions may be associated with suppression of LTD expression in the sensorimotor striatum.

Animals↗
PubMed2003

D-cycloserine facilitates synaptic plasticity but impairs glutamatergic neurotransmission in rat hippocampal slices.

1. The glycine-binding site of the glutamatergic N-methyl-d-aspartate receptor subtype (NMDAr) has been proposed as a putative target for treating cognitive impairments in neurodegenerative disorders and schizophrenia. Although behavioural evidence has been accumulated showing that the partial agonist d-cycloserine (DCS) facilitated learning and memory, physiological mechanisms of the drug still remained to be characterized. In the present study, we have investigated the effects of DCS on glutamatergic neurotransmission and synaptic plasticity in CA1 region of rat hippocampal slices, using extracellular field excitatory postsynaptic potentials. 2. We showed that DCS facilitated NMDAr-mediated synaptic potentials. In addition, we found that the magnitude of NMDAr-dependent long-term depression was significantly enhanced by the agonist, while the threshold for the induction of lasting potentiations was lowered. 3. We found that DCS decreased neurotransmission mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate subtypes of glutamate receptors. This inhibition was not prevented by the gamma-aminobutyric acid GABAA antagonist bicuculline, but was antagonized by the glycine antagonist strychnine. 4. These results, therefore, show opposite effects of DCS on NMDA and non-NMDA synaptic responses within the hippocampus. They also demonstrate that DCS facilitates long-term synaptic plasticity that may support the DCS-induced enhanced cognitive performances.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2003

Effects of clozapine, haloperidol and iloperidone on neurotransmission and synaptic plasticity in prefrontal cortex and their accumulation in brain tissue: an in vitro study.

The mode of action of the antipsychotic drugs clozapine, haloperidol and iloperidone was investigated in layer V of prefrontal cortex slices using extracellular field potential, intracellular sharp-electrode as well as whole-cell voltage clamp recording techniques. Intracellular investigations on a broad range of concentrations revealed that the typical neuroleptic haloperidol at higher concentrations significantly depressed the excitatory postsynaptic component induced by electrical stimulation of layer II. This was not seen with the atypical neuroleptics clozapine and iloperidone. None of the three compounds had any effect on the resting membrane potential, spike amplitude or input resistance at relevant concentrations. Synaptic plasticity was assessed by means of extracellular field potential recordings. Clozapine significantly facilitated the potentiation of synaptic transmission, whereas haloperidol and iloperidone showed no effects. In line with its facilitating effect on synaptic plasticity, it could be demonstrated by whole-cell voltage clamp recordings that clozapine increased N-methyl-D-aspartic acid receptor-mediated excitatory postsynaptic currents in the majority of prefrontal cortical neurones. These investigations were made with neuroleptic drugs applied to the bath in the micromolar concentration range in order to approach clinical brain concentrations that are reached after administration of therapeutic doses. The drug concentrations reached in the slices after the experiments were assessed by means of high-pressure liquid chromatography coupled with mass-spectrometric detection. Surprisingly, drug accumulation in the in vitro preparation was of similar degree as reported in vivo. In conclusion, the typical neuroleptic haloperidol significantly depressed excitatory synaptic transmission in layer V neurones of the prefrontal cortex. In contrast, the two atypical neuroleptics iloperidone and clozapine revealed no depressing effects. This feature of the atypical neuroleptics might be beneficial since a hypofunctionality of this brain area is thought to be linked with the pathophysiology of schizophrenia. Additionally, clozapine facilitated long-term potentiation, which might be linked with the clinically observed beneficial effects on certain cognitive parameters. The clozapine-induced increase of N-methyl-D-aspartic acid receptor-mediated currents suggests that clozapine facilitates the induction of long-term potentiation. Furthermore, the present study points to the importance of considering the significant accumulation of neuroleptic drugs in in vitro studies.

2-Amino-5-phosphonovalerate↗
PubMed1989

Synaptic plasticity at the crayfish opener neuromuscular preparation.

The crayfish opener neuromuscular preparation exhibits most of the plasticities yet described for any synapse, including facilitation, long-term potentiation, presynaptic inhibition, and modulation. Since the presynaptic terminals and postsynaptic muscle fibers can both be intracellularly penetrated, one can now more easily examine the cellular/molecular bases for these plasticities. Data from such studies suggest that facilitation may be influenced by something other than residual free calcium and that presynaptic inhibition is produced by a conductance increase to chloride in the terminals of the excitor axon. Several drugs (ethanol, pentobarbital) have significant effects on these synaptic plasticities over concentration ranges which produce obvious behavioral effects in crayfish and mammals. Hence, this preparation should be a useful model system to determine cellular/molecular bases for various synaptic plasticities and the effects of drugs on these plasticities.

Animals↗
PubMed2006

Increased hippocampal mRNA expression of neuronal synaptic plasticity related genes in mice chronically exposed to toluene at a low-level human occupational-exposure.

Although neurological symptoms in individuals exposed to toluene both inside and outside the homes have been reported well, the chronic effects of low-level toluene-exposure on the hippocampal expression of neuronal synaptic plasticity related genes have not been studied in vivo. In the present study, to understand the possible adult hippocampal neurobiological responses of mice chronic exposure to toluene at a low-level human occupational-exposure, we exposed 10-week-old C3H/HeN female mice to 50 ppm toluene or filtered air for 6 h a day, on 5-consecutive days of a week for 6 and 12 weeks, in a whole-body exposure chamber. Then, by a quantitative real-time PCR method, we investigated the hippocampal mRNA-expression of several genes, functions of which are necessary to maintain the homeostasis of neuronal synaptic plasticity. We observed that chronic exposure of mice to 50 ppm toluene for a longer period (12 weeks) caused a significant up-regulation of NMDA receptor subunit 2B (NMDA NR2B) expression associated with a simultaneous induction of CaMKIV, CREB-1, and FosB/DeltaFosB in the same hippocampal tissues. Our data indicate that the in vivo transcriptional up-regulation of these genes in the adult hippocampus of our experimental mouse model following the chronic exposure to toluene may be an NMDA-receptor related neuroprotective mechanism of gene expression.

Animals↗
PubMed2006

Early development of aberrant synaptic plasticity in a mouse model of Huntington's disease.

Huntington's disease (HD) is a fatal neurodegenerative disorder characterized by progressive motor, psychiatric and cognitive decline. Marked neuronal loss occurs in the cortex and striatum. HD is inherited in an autosomal dominant fashion and caused by a trinucleotide repeat expansion (CAG) in the gene encoding the protein huntingtin. Predictive genetic testing has revealed early cognitive deficits in asymptomatic gene carriers at a time when there is little evidence for cell death, suggesting that impaired cognition results from a cellular or synaptic deficit, such as aberrant synaptic plasticity. Altered hippocampal long-term potentiation has been reported in mouse models of HD; however, the relationship between synaptic dysfunction and phenotype progression has not previously been characterized. We examined the age-dependency of aberrant hippocampal synaptic plasticity in the R6/1 mouse model of HD. Long-term depression (LTD) is a developmentally regulated form of plasticity, which normally declines by early adulthood. Young R6/1 mice follow the same pattern of LTD expression as controls, in that they express LTD in the first weeks of life, and then lose the ability with age. Unlike controls, R6/1 synapses later regain the ability to support LTD. This is associated with nuclear localization of mutant huntingtin, but occurs months prior to the formation of nuclear aggregates. We present the first detailed description of a progressive derailment of a functional neural correlate of cognitive processing in HD.

Aging↗
PubMed2005

The apoE receptor apoER2 is involved in the maintenance of efficient synaptic plasticity.

ApoER2 is one of the major receptors for ApoE in the brain, and has been shown to be involved not only in lipoprotein endocytosis, as other members of the LDL receptor family of receptors, but also in various cellular functions such as signalling and cellular guidance. By using a model of synaptic plasticity in mice lacking none, one or two alleles of the apoER2 gene, we investigated the implication of such a receptor deficiency on the remodelling process. Our results indicate that animals lacking apoER2 express higher levels of brain APP, as well as both key amyloid peptides, while apoE levels are slightly lower. Following entorhinal cortex lesioning, apoE levels increase in the deafferented hippocampus, while a delay in the increase of APP was observed. Hippocampal amyloid levels are also increased in response to the lesion, and highly potentiated by the complete absence of apoER2 gene. The results suggest a significant role for apoER2 in signalling various proteins in response to massive deafferentation and may participate in maintaining efficient synaptic plasticity and dendritic remodelling.

Amyloid beta-Peptides↗