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Results for “synaptic plasticity”

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PubMed2003

Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory.

Plasticity of the nervous system is dependent on mechanisms that regulate the strength of synaptic transmission. Excitatory synapses in the brain undergo long-term potentiation (LTP) and long-term depression (LTD), cellular models of learning and memory. Protein phosphorylation is required for the induction of many forms of synaptic plasticity, including LTP and LTD. However, the critical kinase substrates that mediate plasticity have not been identified. We previously reported that phosphorylation of the GluR1 subunit of AMPA receptors, which mediate rapid excitatory transmission in the brain, is modulated during LTP and LTD. To test if GluR1 phosphorylation is necessary for plasticity and learning and memory, we generated mice with knockin mutations in the GluR1 phosphorylation sites. The phosphomutant mice show deficits in LTD and LTP and have memory defects in spatial learning tasks. These results demonstrate that phosphorylation of GluR1 is critical for LTD and LTP expression and the retention of memories.

Animals↗
PubMed1999

Synaptic plasticity in cortical systems.

Recent studies indicate that synapse addition and/or loss is associated with different types of learning. Other factors influencing synaptogenesis and synapse loss include neurotrophins, hormones, and the induction of long-term potentiation. An emerging view of synaptic plasticity suggests that local neurotrophin action and synaptically associated protein synthesis may promote synaptic remodelling and changes in receptor expression or activation.

Animals↗
PubMed1995

Modulation of ion currents and regulation of transmitter release in short-term synaptic plasticity: the rise and fall of the action potential.

Up and down-regulation of calcium and potassium conductances are associated with several forms of short-term synaptic modulation. Detailed investigation of synaptic plasticity in the marine gastropod Aplysia, and in other mollusks, indicates that synaptic transmission can be influenced in a number of ways by modulatory neurotransmitters acting through several second-messenger cascades. Modulation at the synapse itself occurs by means of the regulation of calcium current as well as through effects on processes directly involved in transmitter mobilization and exocytosis. Modulation of potassium current plays a major role in controlling neuronal excitability and may contribute to a lesser extent to the regulation of transmitter release through actions on the resting potential and on action potential configuration.

Action Potentials↗
PubMedDate not supplied

[Short term synaptic plasticity].

INTRODUCTION: At many chemical synapses, the amount of transmitter released by each action potential can increase or decrease markedly after the onset of specific temporal patterns of activity. OBJECTIVES: This review focuses on mechanisms and functions of short term presynaptic plasticity that last from milliseconds to minutes. The short term enhancement of neurotransmitter release is due to three calcium dependent presynaptic processes differing in their durations: about one second or less (facilitation), about 30 seconds (augmentation) and several minutes (post tetanic potentiation). These forms of short term potentiation are usually attributed to a transient elevation in presynaptic calcium ions (Ca2+) concentration following the arrival of the action potential. Otherwise, presynaptic depression processes, as well as the facilitation ones, depend on neurotransmitter release probability. Thus, synapses with high release probability show few facilitation and are easily depressed because of their ability to deplete faster all synaptic vesicles of the ready releasable pool. CONCLUSIONS: Short term synaptic plasticity appears to serve as a flexible mechanism for temporal information processing in higher cortical integration.

Action Potentials↗
PubMed2002

Spike-timing-dependent synaptic plasticity - the long road towards understanding neuronal mechanisms of learning and memory.

Depending on the precise temporal relationship between their spiking activities, connections between neurons could be modified in opposite directions. Although the functional implications of this spike-timing-dependent plasticity are not clear, several theoretical studies have indicated that it could underlie important effects such as sequence learning, predictive learning and balancing excitation and inhibition. To explore fully this novel form of synaptic plasticity, it is crucial to understand how the modification builds up over the consecutive spikes of presynaptic and postsynaptic neurons. In the absence of solid data, many theorists assumed a linear summation model. However, recent experiments specifically devised to study this issue have demonstrated that the effects of the consecutive spikes on the overall modification steadily decline, indicating strong non-linearities in the corresponding learning rules.

Animals↗
PubMed1997

Seizures, memory and synaptic plasticity.

Electrophysiological studies of the rodent hippocampus show that repeated seizure activity has a profound, deleterious effect on an important form of synaptic plasticity (long-term potentiation, LTP) which has been suggested to underlie memory formation. It appears that seizure activity incrementally causes an indiscriminate and widespread induction of long-term potentiation, consuming and thereby reducing overall hippocampal plasticity available for information processing. Consistent with this finding, severe deficits in a form of learning known to be mediated by hippocampal function are observed in rat subjected to repeated electroconvulsive seizures (ECS). The effect on synaptic function gradually resolves over a period of around 40 days, paralleling the time course of the transitory cognitive impairment seen following electrical seizure induction (ECT) in humans being treated for severe affective disorder. The effect is likely to be mediated by NMDA receptor activation during seizure activity, as the phenomenon can be prevented by the administration of a non-competitive NMDA receptor associated channel blocker (ketamine) immediately before seizure induction. The mechanisms described may account for the inter-ictal cognitive disturbance observed in patients suffering from poorly controlled epilepsy.

Animals↗
PubMed2005

In vivo investigation of genome activity and synaptic plasticity of neurons in snails during learning.

The present report describes in vivo investigations of genome activity and its role in the mechanisms forming long-term synaptic plasticity in defensive behavior command neuron LPl1 during the acquisition of nociceptive sensitization by common snails. Transcription processes were recorded using SYTO 16, a specific fluorescent indicator of DNA activity, along with in vivo computer image analysis. Studies in control snails showed that application of nociceptive stimuli to the head led to biphasic changes in the bioelectrical responses of neurons to tactile and chemical stimulation--depression of responses in the short-term stage (during the 1 h after training) and their facilitation during the long-term stage of sensitization (more than 24 h). There were marked increases in fluorescence over the nucleus of the command neuron stained with SYTO 16 at 15-20 min from the start of training, this lasting 4-5 h. Acquisition of sensitization in the presence of the RNA synthesis inhibitor actinomycin D (20 microM) to the neuron led to the complete elimination of changes in fluorescence and synaptic facilitation in the responses of LPl1 to sensory stimulation in the long-term stage of sensitization but had no effect during the short-term stage of sensitization. Actinomycin D given 30 min after the end of acquisition of sensitization (1 h after the start) had no effect on the dynamics of fluorescence or synaptic facilitation. Thus, the acquisition of nociceptive sensitization is accompanied by a rapid (within 15-20 min) activation of the DNA of neuron LPl1 and subsequent (about 1 h) display of long-term synaptic facilitation. Induction of both processes was suppressed by the RNA synthesis inhibitor over a relatively short time period--1 h from the moment at which training started.

Action Potentials↗
PubMed2006

Matrix metalloproteinase-3 expression profile differentiates adaptive and maladaptive synaptic plasticity induced by traumatic brain injury.

The interaction between extracellular matrix (ECM) and regulatory matrix metalloproteinases (MMPs) is important in establishing and maintaining synaptic connectivity. By using fluid percussion traumatic brain injury (TBI) and combined TBI and bilateral entorhinal cortical lesion (TBI + BEC), we previously demonstrated that hippocampal stromelysin-1 (MMP-3) expression and activity increased during synaptic plasticity. We now report a temporal analysis of MMP-3 protein and mRNA response to TBI during both degenerative (2 day) and regenerative (7, 15 day) phases of reactive synaptogenesis. MMP-3 expression during successful synaptic reorganization (following unilateral entorhinal cortical lesion; UEC) was compared with MMP-3 expression when normal synaptogenesis fails (after combined TBI + BEC insult). Increased expression of MMP-3 protein and message was observed in both models at 2 days postinjury, and immuohistochemical (IHC) colocalization suggested that reactive astrocytes contribute to that increase. By 7 days postinjury, model differences in MMP-3 were observed. UEC MMP-3 mRNA was equivalent to control, and MMP-3 protein was reduced within the deafferented region. In contrast, enzyme mRNA remained elevated in the maladaptive TBI + BEC model, accompanied by persistent cellular labeling of MMP-3 protein. At 15 days survival, MMP-3 mRNA was normalized in each model, but enzyme protein remained higher than paired controls. When TBI + BEC recovery was enhanced by the N-methyl-D-aspartate antagonist MK-801, 7-day MMP-3 mRNA was significantly reduced. Similarly, MMP inhibition with FN-439 reduced the persistent spatial learning deficits associated with TBI + BEC insult. These results suggest that MMP-3 might differentially affect the sequential phases of reactive synaptogenesis and exhibit an altered pattern when recovery is perturbed.

Adaptation, Physiological↗
PubMed2004

Behavioral stress modifies hippocampal synaptic plasticity through corticosterone-induced sustained extracellular signal-regulated kinase/mitogen-activated protein kinase activation.

The induction of hippocampal long-term synaptic plasticity is exquisitely sensitive to behavioral stress, but the underlying mechanisms are still unclear. We report here that hippocampal slices prepared from adult rats that had experienced unpredictable and inescapable restraint tail-shock stress showed marked impairments of long-term potentiation (LTP) in the CA1 region. The same stress promoted the induction of long-term depression (LTD). These effects were prevented when the animals were given the glucocorticoid receptor antagonist 11beta, 17beta-11[4-(dimethylamino)phenyl]-17-hydroxy-17-(1-propynyl)-estra-4-9-dien-3-one before the stress. Immunoblotting analyses revealed that stress induced a profound and prolonged extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK1/2 MAPK) hyperphosphorylation through small GTPase Ras, Raf-1, and MAPK kinase 1/2 (MEK1/2). Furthermore, the stress effects were obviated by the intrahippocampal injection of specific inhibitors of MEK1/2 (U0126), protein kinase C (bisindolylmaleimide I), tyrosine kinase (K252a), and BDNF antisense oligonucleotides. These results suggest that the effects of stress on LTP and LTD originate from the corticosterone-induced sustained activation of ERK1/2-coupled signaling cascades.

Adrenocorticotropic Hormone↗
PubMed2005

Pathological synaptic plasticity in the striatum: implications for Parkinson's disease.

Repetitive stimulation of the corticostriatal pathway can cause either a long-lasting increase, or an enduring decrease in synaptic strength, respectively referred to as long-term potentiation (LTP), and long-term depression (LTD), both requiring a complex sequence of biochemical events. Once established, LTP can be reversed to control levels by a low-frequency stimulation (LFS) protocol, an active phenomenon defined "synaptic depotentiation", required to erase redundant information. In the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease (PD), striatal synaptic plasticity has been shown to be impaired, though chronic treatment with l-dopa was able to restore it. Interestingly, a consistent number of l-dopa-treated animals developed involuntary movements, resembling human dyskinesias. Strikingly, electrophysiological recordings from the dyskinetic group of rats demonstrated a selective impairment of synaptic depotentiation. This survey will provide an overview of plastic changes occurring at striatal synapses. The potential relevance of these findings in the control of motor function and in the pathogenesis both of Parkinson's disease and l-dopa-induced motor complications will be discussed.

Animals↗
PubMed2001

Determinants of spike timing-dependent synaptic plasticity.

Recent studies show that the precise timing of presynaptic inputs and postsynaptic action potentials influences the strength and sign of synaptic plasticity. In this issue of Neuron, Sjöström and colleagues (2001) determine how this so-called spike timing-dependent plasticity depends on the frequency and strength of the presynaptic inputs.

Action Potentials↗
PubMed1997

Molecular genetic analysis of synaptic plasticity, activity-dependent neural development, learning, and memory in the mammalian brain.

Recently, dozens of mutant mice generated with gene targeting or transgenic technologies have been shown to exhibit a distinct set of impairments in the brain and behavior. In this review, we discuss how studies of mutant mice have helped elucidate the mechanisms that underlie synaptic plasticity and the relationship of these synaptic mechanisms to the activity-dependent phase of neural development and learning and memory. We focus on the recent progress in the analysis of whisker-related pattern formation, elimination of climbing fibers, long-term potentiation, long-term depression, and various learning and memory tasks in mutant mice.

Animals↗
PubMed2003

Galanin regulates spatial memory but not visual recognition memory or synaptic plasticity in perirhinal cortex.

It has previously been shown that the neuropeptide galanin plays a role in the age-dependent regulation of hippocampal synaptic plasticity and spatial memory. Here, we further extend these studies by demonstrating that galanin knockout mice also have deficits in an object-in-place spatial memory task. In contrast however, there is no deficit in single item object recognition memory, a memory that depends on perirhinal cortex. Furthermore, in perirhinal cortex slices there are no differences in activity-dependent long-term potentiation or depotentiation, nor in muscarinic receptor-dependent long-term depression between galanin knockout mice and wild-type litter-mates. Therefore, these results suggest that galanin has a differential role in hippocampal-dependent and perirhinal cortex-dependent memory.

Animals↗
PubMed2003

The serotonergic modulation of synaptic plasticity in the rat hippocampo-medial prefrontal cortex pathway.

The ability of the serotonergic (5-HTergic) system to affect the hippocampo-medial prefrontal cortex (mPFC) synaptic properties was examined in rats with lesions of 5-HTergic neurons. Intracerebroventricular injections of 5,7-dihydroxytryptamine (5,7-DHT) resulted in selective depletion of 5-HT and 5-hydroxyindoleacetic acid in the cerebral cortex, hippocampus and raphe regions. The 5,7-DHT-lesioned rat had no changes in basal synaptic transmission in the hippocampo-mPFC pathway. Conversely, we observed the augmentation of short-term synaptic plasticity, i.e. paired-pulse facilitation, when compared with sham-operated rats in this pathway. The magnitude of long-term potentiation (LTP) was significantly augmented in 5,7-DHT-lesioned rats. This augmentation of hippocampo-mPFC LTP had a significant correlation with the degree of cortical 5-HT levels. These results suggest that the 5-HTergic system may modulate plastic properties at the hippocampal-mPFC synapses in vivo.

5,7-Dihydroxytryptamine↗
PubMed2002

Synchrony arising from a balanced synaptic plasticity in a network of heterogeneous neural oscillators.

We investigate the dynamics of a recurrent network of coupled heterogeneous neural oscillators with experimentally observed spike-timing-dependent synaptic plasticity. We show both theoretically and by computer simulations that, in a regime of a balance between synaptic potentiation and depression, the network of such oscillators converges to a stable synchronous state. The stability of this state is fostered by flexible synaptic weights which adjust themselves based on the relative timing of firing of pre- and postsynaptic oscillators.

Animals↗
PubMed2006

Analysis of knock-out mice to determine the role of HPC-1/syntaxin 1A in expressing synaptic plasticity.

The protein HPC-1/syntaxin 1A is abundantly expressed in neurons and localized in the neuronal plasma membrane. It forms a complex with SNAP-25 (25 kDa synaptosomal-associated protein) and VAMP-2 (vesicle-associated membrane protein)/synaptobrevin called SNARE (a soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) complex, which is considered essential for synaptic vesicle exocytosis; thus, HPC-1/syntaxin 1A is considered crucial for synaptic transmission. To examine the physiological function of HPC-1/syntaxin 1A in vivo, we produced knock-out (KO) mice by targeted gene disruption. Although HPC-1/syntaxin 1A expression was completely depleted without any effect on the expression of other SNARE proteins, the KO mice were viable. They grew normally, were fertile, and displayed no difference in appearance compared with control littermate. In cultured hippocampal neurons derived from the KO mice, the basic synaptic transmission in vitro was normal. However, the mutant mice had impaired long-term potentiation in the hippocampal slice. Also, although KO mice exhibited normal spatial memory in the hidden platform test, consolidation of conditioned fear memory was impaired. Interestingly, the KO mice had impaired conditioned fear memory extinction. These observations suggest that HPC-1/syntaxin 1A may be closely related to synaptic plasticity.

Animals↗
PubMed2002

Functional improvement after motor training is correlated with synaptic plasticity in rat thalamus.

The goals of this study were to determine whether functional outcome after motor training in rats was linked to synaptic plasticity in thalamus, and whether the Rota-rod apparatus, widely used to test motor function, could be used as an easy and quantitative motor skill training procedure. Adult female Sprague-Dawley rats (n = 39) were evaluated under three training conditions: 1. Movement requiring balance and coordination skills on Rota-rod; 2. simple exercise on treadmill; 3. nontrained controls. Motor function was evaluated by a series of motor tests (foot fault placing, parallel bar crossing, rope and ladder climbing) before and 14 or 28 days after training procedure. Synaptic strength in brain was assessed by synaptophysin immunocytochemistry. After 14 days of training, Rota-rod-trained animals significantly (p < 0.01) improved motor performance, compared to treadmill and nontrained animals. Animals with up to 28 days of simple exercises on the treadmill did not show a significantly improved performance on most motor tasks, except for an improvement in foot fault placing. Intensive synaptophysin immunoreactivity was present in the right but not the left mediodorsal and ventromedial nuclei of thalamus in Rota-rod-trained rats at 14 and 28 days, and in treadmill-trained rats at 28 days. The data suggested that functional outcome is effectively improved by motor skill training rather than by simple exercises, and this may be related, at least partially, to uniquely lateralized synaptogenesis in the thalamus. Both Rota-rod and treadmill could be quantitatively used in rats for motor training of different complexity.

Animals↗
PubMed1985

Chronic dietary choline modulates synaptic plasticity in the cerebellar glomeruli of aging mice.

A morphometric investigation was carried out on ethanolic phosphotungstic acid (E-PTA) stained synaptic junctions in the cerebellar glomeruli of adult, old, old choline-deficient and old choline-supplemented mice. Numerical (Nv) and surface (Sv) density as well as average length (L) of the synapses were calculated on 100 pictures per group. A significant reduction of Nv and Sv, as well as an increase of L was found during aging. Choline deficient animals did not show any change as compared to old animals of the same age. In choline supplemented mice Nv and Sv were significantly increased and L significantly decreased, respectively, as compared to old control littermates. No difference was found between adult and choline supplemented mice. In the cerebellar glomeruli only a small fraction of fibers are cholinergic, therefore the present findings support the idea that dietary choline can influence systems other than cholinergic. The possible role of choline supplementation in the modulation of synaptic plasticity via the synthesis and/or turnover of neuronal membrane choline phospholipids, is discussed.

Animals↗