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Results for “synaptic plasticity”

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At least 307 records · Page 17Linked to original sources
PubMed2003

Prenatal morphine exposure suppresses mineralocorticoid receptor-dependent basal synaptic transmission and synaptic plasticity in the lateral perforant path in adult male rats.

The effects of prenatal morphine exposure (E11-18) on mineralocorticoid receptor (MR) modulation of synaptic plasticity were investigated in the lateral perforant path (LPP)-dentate gyrus granule cell synaptic system. Hippocampal slices were prepared from adult, prenatally saline- or morphine-exposed male rats. One hour prior to decapitation, some adult male rats were injected subcutaneously with saline or the MR antagonist, canrenoic acid (50 mg/kg). LPP was stimulated with high-frequency (2x100 Hz/0.5 s) and short-term plasticity (STP) and long-term potentiation (LTP) were evaluated at 5 and 30 min poststimulation, respectively. Prenatally saline-exposed male rats injected with saline 1 h prior to decapitation showed significantly higher levels of baseline, STP, and LTP than prenatally saline-exposed, canrenoic acid-treated males. In contrast, prenatally morphine-exposed male rats regardless of saline or canrenoic acid injection 1 h prior to decapitation were comparable in their baseline, STP, and LTP activities. Thus, the results demonstrate that canrenoic acid decreases the efficacy of the basal synaptic transmission in the LPP as well as suppresses synaptic plasticity in saline-exposed males. However, in adult morphine-exposed male rats, canrenoic acid has no other or further effects than a saline treatment suggesting that prenatal morphine exposure suppresses MR-dependent basal synaptic transmission as well as synaptic plasticity.

Animals↗
PubMed1997

Age-associated changes in Ca(2+)-dependent processes: relation to hippocampal synaptic plasticity.

Altered calcium (Ca2+) homeostasis is thought to play a key role in aging and neuropathology resulting in memory deficits. Several forms of hippocampal synaptic plasticity are dependent on Ca2+, providing a potential link between altered Ca2+ homeostasis and memory deficits associated with aging. The current study reviews evidence for Ca2+ dysregulation during aging which could interact with Ca(2+)-dependent synaptic plasticity. The authors suggest that changes in Ca2+ regulation could adjust the thresholds for synaptic modification, favoring processes for depression of synaptic strength during aging.

Aging↗
PubMed1999

Deletion of the ryanodine receptor type 3 (RyR3) impairs forms of synaptic plasticity and spatial learning.

Deletion of the ryanodine receptor type 3 (RyR3) results in specific changes in hippocampal synaptic plasticity, without affecting hippocampal morphology, basal synaptic transmission or presynaptic function. Robust long-term potentiation (LTP) induced by repeated, strong tetanization in the CA1 region and in the dentate gyrus was unaltered in hippocampal slices in vitro, whereas weak forms of plasticity generated by either a single weak tetanization or depotentiation of a robust LTP were impaired. These distinct physiological deficits were paralleled by a reduced flexibility in re-learning a new target in the water-maze. In contrast, learning performance in the acquisition phase and during probe trial did not differ between the mutants and their wild-type littermates. In the open-field, RyR3(-/-) mice displayed a normal exploration and habituation, but had an increased speed of locomotion and a mild tendency to circular running. The observed physiological and behavioral effects implicate RyR3-mediated Ca(2+) release in the intracellular processes underlying spatial learning and hippocampal synaptic plasticity.

Animals↗
PubMed2001

[Calcium dependent forms of synaptic plasticity in cerebellar Purkinje cells].

Elevation of intracellular calcium concentration ([Ca(2+)](i)) induces several forms of long-term synaptic plasticity in cerebellar Purkinje cells (PCs). These include (1) long-term depression (LTD) at parallel fiber (PF) to PC synapses, (2) LTD at climbing fiber (CF) to PC synapses, (3) long-term potentiation (LTP) at synapses from inhibitory interneurons (rebound potentiation). The current knowledge about calcium dependency for these forms of synaptic plasticity is described in this chapter. (1) Induction of PF-LTD is dependent on elevation of [Ca(2+)](i), that derives from two distinct sources. One is through voltage-dependent calcium channel (VDCC). A CF stimulation leads to elevation of [Ca(2+)](i) due to activation of VDCCs. The other is from the internal calcium store. PFs stimulation activates metabotropic glutamate receptor subtype 1 (mGluR1). It leads to production of inositol-1,4,5-triphosphate (IP(3)) and diacylglycerol (DG) which cause calcium release from internal stores and activation of protein kinase C, respectively. The conjunctive activation of PF and CF inputs is necessary for PF-LTD. (2) LTD at CF to PC synapses (CF-LTD) is induced by the mechanisms similar to those involved in PF-LTD. CF-LTD requires elevation of [Ca(2+)](i) and activation of the mGluR1 to PKC cascade. (3) Rebound potentiation is induced by transient elevation of [Ca(2+)](i) due to activation of VDCCs or IP3-mediated calcium release from internal stores. Elevation of [Ca(2+)](i) activates calcium/ calmodulin-dependent protein kinase II and leads to persistent up-regulation of postsynaptic GABAA receptor function. At the three types of synapses described above, elevation of [Ca(2+)](i) also causes short-term depression of neurotransmitter release from presynaptic terminals. Recent studies demonstrate that transient elevation of [Ca(2+)](i) produces endocannabinoids in PCs that act retrogradely onto presynaptic terminals and suppress neurotransmitter release.

English Abstract↗
PubMed1999

Trophic regulation of synaptic plasticity.

Trophins are now known to acutely regulate synaptic plasticity, in addition to exerting long-recognized actions on neuronal survival and development. To begin elucidating underlying mechanisms, cultured dissociated hippocampal neurons were examined by whole-cell patch-clamp recording. BDNF (brain derived neurotrophic factor) specifically and selectively increased the integrated synaptic current twofold within five minutes. The effect was mediated postsynaptically by the trkB receptor and intracellular phosphorylation-dependent mechanisms. Iontophoresis combined with patch-clamp recording indicated that BDNF increased activity of NMDA (N-methyl-D-aspartate) receptors. Single channel-channel recording indicated that BDNF increased channel open probability by increasing opening frequency. In parallel, the trophin specifically increased phosphorylation of NR1 and NR2B subunits of NMDA receptors in the postsynaptic density, providing potential mechanisms eliciting receptor activation. A model is proposed in which activity-driven experience activates specific BDNF gene promoters, leading to enhanced transcription, elevated trophin levels, postsynaptic NMDA receptor activation and increased synaptic transmission. These sequential mechanisms may contribute to enhanced long-term potentiation, a correlate of learning and memory.

Animals↗
PubMed2006

Novelty exploration elicits a reversal of acute stress-induced modulation of hippocampal synaptic plasticity in the rat.

Acute behavioural stress has been recognized as a strong influence on the inducibility of hippocampal long-term synaptic plasticity. We have reported previously that in adult male rats, acute behavioural stress impairs long-term potentiation (LTP) but enhances long-term depression (LTD) in the hippocampal CA1 region. In this study we report that the effects of stress on LTP and LTD were reversed when animals were introduced into a novel 'stimulus-rich' environment immediately after the stress. Novelty exploration-induced reversal of stress effects was prevented when the animals were given the NMDA receptor antagonist D-(-)-2-amino-5-phosphonopentanoic acid, the cholinergic antagonist atropine and the protein phosphatase (PP) 2B inhibitors cyclosporin A and cypermethrin, but not the alpha1-adrenergic antagonist prazosin, the beta-adrenergic antagonist propranolol or the PP1/2A inhibitor okadaic acid, respectively before being subjected to the novel environment. In addition, the ability of novelty exploration to reverse the stress effects was mimicked by a direct application of the cholinergic agonist carbachol. Exposure to the novel environment following stress was accompanied by the activation of both PP2B and striatal-enriched tyrosine phosphatase (STEP). Taken together, these findings suggest that the activation of the cholinergic system and, in turn, the triggering of an NMDA receptor-mediated activation of PP2B to increase STEP activity appear to mediate the novelty exploration-induced reversal of stress-related modulation of hippocampal long-term synaptic plasticity.

Animals↗
PubMed2002

Hebbian spike-driven synaptic plasticity for learning patterns of mean firing rates.

Synaptic plasticity is believed to underlie the formation of appropriate patterns of connectivity that stabilize stimulus-selective reverberations in the cortex. Here we present a general quantitative framework for studying the process of learning and memorizing of patterns of mean spike rates. General considerations based on the limitations of material (biological or electronic) synaptic devices show that most learning networks share the palimpsest property: old stimuli are forgotten to make room for the new ones. In order to prevent too-fast forgetting, one can introduce a stochastic mechanism for selecting only a small fraction of synapses to be changed upon the presentation of a stimulus. Such a mechanism can be easily implemented by exploiting the noisy fluctuations in the pre- and postsynaptic activities to be encoded. The spike-driven synaptic dynamics described here can implement such a selection mechanism to achieve slow learning, which is shown to maximize the performance of the network as an associative memory.

Action Potentials↗
PubMed2001

Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory.

Calcineurin is a calcium-dependent protein phosphatase that has been implicated in various aspects of synaptic plasticity. By using conditional gene-targeting techniques, we created mice in which calcineurin activity is disrupted specifically in the adult forebrain. At hippocampal Schaffer collateral-CA1 synapses, LTD was significantly diminished, and there was a significant shift in the LTD/LTP modification threshold in mutant mice. Strikingly, although performance was normal in hippocampus-dependent reference memory tasks, including contextual fear conditioning and the Morris water maze, the mutant mice were impaired in hippocampus-dependent working and episodic-like memory tasks, including the delayed matching-to-place task and the radial maze task. Our results define a critical role for calcineurin in bidirectional synaptic plasticity and suggest a novel mechanistic distinction between working/episodic-like memory and reference memory.

Animals↗
PubMed2003

Suppression of L-type voltage-gated calcium channel-dependent synaptic plasticity by ethanol: analysis of miniature synaptic currents and dendritic calcium transients.

Intoxicating concentrations of ethanol inhibit N-methyl-d-aspartate (NMDA) receptor-dependent long-term potentiation, an interaction thought to underlie a major component of the central nervous system actions of ethanol. Another form of synaptic potentiation involving activation of L-type dihydropyridine-sensitive voltage-gated calcium channels (VGCCs) has been described, but very little information concerning ethanol effects on VGCC-dependent synaptic potentiation is available. Here, we assessed ethanol effects on VGCC-dependent synaptic potentiation using whole cell patch-clamp recordings of alpha-amino-3-hydroxy-5-methyl-4-soxazolepropionic acid (AMPA) receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in area CA1 of the rat hippocampus. No potentiation was observed in artificial cerebrospinal fluid containing 2 to 3 mM Ca2+, but marked potentiation of mEPSCs was consistently observed in 4 mM Ca2+ and with patch pipettes containing an ATP-regenerating system. This potentiation was insensitive to the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid, whereas it was completely blocked the L-type VGCC antagonist nifedipine. Potentiation was also blocked dose dependently by bath application of ethanol (25-75 mM), which had no effect on baseline mEPSC amplitude or frequency. The synaptic potentiation involved enhancement of both presynaptic and postsynaptic components because significant increases in both the frequency and amplitude of AMPA mEPSCs were observed. Ethanol inhibition of VGCC-dependent synaptic potentiation seemed to occur at the induction step because both the increases in mEPSC frequency and amplitude were affected. To address that question more directly, we used fluorescent imaging of synaptically evoked dendritic calcium events, which displayed a similarly marked ethanol sensitivity. Thus, ethanol modulates fast excitatory synaptic transmission by inhibiting the induction of an NMDA receptor-independent form of synaptic potentiation observed at excitatory synapses on central neurons.

Animals↗
PubMed2000

Estrogen receptors and insulin-like growth factor-I receptors mediate estrogen-dependent synaptic plasticity.

Previous studies have shown that estradiol induces a transient disconnection of axo-somatic inhibitory synapses in the hypothalamic arcuate nucleus of adult ovariectomized rats. The synaptic disconnection is accompanied by an increase in the levels of insulin-like growth factor-I (IGF-I) in the arcuate nucleus, suggesting that IGF-I signaling may be involved in the estrogen-induced synaptic plasticity. The role of estrogen receptors and IGF-I receptors in the synaptic changes has been studied by assessing the number of axo-somatic synapses in ovariectomized rats treated with intracerebroventricular administration of the estrogen receptor antagonist ICI 182,780 and the IGF-I receptor antagonist JBI to ovariectomized rats. Estradiol administration resulted in a significant decrease in the number of axo-somatic synapses on arcuate neurons in control ovariectomized rats. Both the estrogen receptor antagonist and the IGF-I receptor antagonist blocked the estrogen-induced synaptic decrease. This finding suggest that estrogen-induced synaptic plasticity in the arcuate nucleus is dependent on the activation of both estrogen receptors and IGF-I receptors.

Animals↗
PubMed2006

Tissue-type plasminogen activator: a multifaceted modulator of neurotransmission and synaptic plasticity.

For over a decade, tissue-type plasminogen activator (t-PA), a serine protease classically known for its profibrinolytic role in the vasculature, has been implicated in numerous aspects of the synaptic plasticity process. But despite being the most intensively studied protease of the CNS, the mechanisms and molecular mediators behind the action of t-PA on synaptic efficacy remain largely undefined. Rather than examine the role of t-PA in proteolytic remodeling of the synaptic extracellular matrix, this review will focus on the evidence that defines t-PA as a direct modulator of neurotransmission and synaptic plasticity by impacting on glutamatergic and dopaminergic pathways.

Animals↗
PubMed2005

Short-term synaptic plasticity in rabbit pancreatic ganglia.

The extrinsic innervation of the pancreas converges on a plexus of intrinsic pancreatic ganglia whose cholinergic neurons innervate acini, ducts, islets and blood vessels. Therefore, understanding ganglionic transmission is essential for understanding neural control of pancreatic secretion. Intracellular recordings of nicotinic fast excitatory postsynaptic potentials (fEPSPs) and action potentials (APs) were used to characterize and compare transmission in ganglia from the head/neck and body regions of the rabbit pancreas. Paired-pulse facilitation (PPF) or depression (PPD) of fEPSPs was observed in ganglia from both regions with PPF peaking and disappearing at shorter inter-stimulus intervals than PPD. PPF was most frequent in the head/neck (60%) and PPD (50%) in the body. Repetitive stimulation (10 Hz/5 s) evoked multiple forms of mid- and post-train plasticity. Facilitation during the first 1-2 s of train stimulation was reduced or reversed with continued stimulation due to development of synaptic depression and mid-train depression was of greater magnitude in the head/neck region. A brief (approximately 10 s) post-train augmentation was followed by a 1-2 min post-train depression that appeared to result from inhibition of ACh release. Regional differences in the frequency, magnitude, or duration of all forms of synaptic plasticity suggested regional differences in the extrinsic innervation patterns and possibly the function of pancreatic ganglia. In conclusion, rabbit pancreatic ganglia exhibit multiple forms of short-term synaptic plasticity that markedly alter the probability of postsynaptic firing, consistent with these ganglia being critical sites of synaptic integration and autonomic regulation of pancreatic secretion.

Animals↗
PubMed2002

Gene control of synaptic plasticity and memory formation: implications for diseases and therapeutic strategies.

There has been nearly a century of interest in the idea that information is stored in the brain as changes in the efficacy of synaptic connections between neurons that are activated during learning. The discovery and detailed report of the phenomenon generally known as long-term potentiation opened a new chapter in the study of synaptic plasticity in the vertebrate brain, and this form of synaptic plasticity has now become the dominant model in the search for the cellular and molecular bases of learning and memory. Accumulating evidence suggests that the rapid activation of the genetic machinery is a key mechanism underlying the enduring modification of neural networks required for the laying down of memory. Here we briefly review these mechanisms and illustrate with a few examples of animal models of neurological disorders how new knowledge about these mechanisms can provide valuable insights into identifying the mechanisms that go awry when memory is deficient, and how, in turn, characterisation of the dysfunctional mechanisms offers prospects to design and evaluate molecular and biobehavioural strategies for therapeutic prevention and rescue.

Aging↗
PubMed2006

Impaired synaptic plasticity in a rat model of tuberous sclerosis.

Tuberous sclerosis complex (TSC) is a common hereditary disorder caused by mutations in either the TSC1 or TSC2 genes, and characterized by severe epilepsy, cerebral hamartomas and mental retardation. We have used rats that are heterozygous for an autosomal-dominant germline mutation in the TSC2 gene (TSC2+/- rats) to examine the consequences of TSC2 mutations for hippocampal synaptic plasticity. While basal synaptic transmission in the Schaffer collateral-CA1 synapse was not altered, paired-pulse plasticity was significantly enhanced in TSC2+/- rats (interpulse intervals 20-200 ms). Moreover, TSC2+/- rats exhibited a marked reduction of different forms of synaptic plasticity. Long-term potentiation (LTP) elicited following high-frequency tetanization of Schaffer collaterals was significantly decreased from 1.45 +/- 0.05-fold potentiation to 1.15 +/- 0.04 (measured after 60 min). This difference in LTP levels between TSC2+/- and wild-type rats also persisted in the presence of the gamma-aminobutyric acid (GABA)(A) receptor antagonist bicuculline. In addition to changed LTP, the level of long-term depression (LTD) elicited by different forms of low-frequency stimulation was significantly less in TSC2+/- rats. These results suggest that TSC2 mutations may cause hippocampal synapses to lose much of their potential for activity-dependent synaptic modification. An understanding of the underlying molecular pathways may suggest new therapeutic approaches aimed at inhibiting the development of the profound mental retardation in TSC.

Animals↗
PubMed2000

Intracellular trafficking of AMPA receptors in synaptic plasticity.

Modification of ligand-gated receptor function at the postsynaptic domain is one of the most important mechanisms by which the efficacy of synaptic transmission in the nervous system is regulated. Traditionally, these types of modifications have been thought to be achieved mainly by altering the channel-gating properties or conductance of the receptors. However, recent evidence suggests that AMPA (alpha-amino-3-hydroxyl-5-methyl-4-isoxayolepropionic acid)-type ligand-gated glutamate receptors are continuously recycling between the plasma membrane and the intracellular compartments via vesicle-mediated plasma membrane insertion and clathrin-dependent endocytosis. Regulation of either receptor insertion or endocytosis results in a rapid change in the number of these receptors expressed on the plasma membrane surface and in the receptor-mediated responses, thereby playing an important role in mediating certain forms of synaptic plasticity. Thus, controlling the number of postsynaptic receptors by regulating the intracellular trafficking and plasma membrane expression of the postsynaptic receptors may be a common and important mechanism of synaptic plasticity in the mammalian central nervous system.

Cell Line↗
PubMed2001

Synaptic plasticity in the medial vestibular nuclei: role of glutamate receptors and retrograde messengers in rat brainstem slices.

The analysis of cellular-molecular events mediating synaptic plasticity within vestibular nuclei is an attempt to explain the mechanisms underlying vestibular plasticity phenomena. The present review is meant to illustrate the main results, obtained in vitro, on the mechanisms underlying long-term changes in synaptic strength within the medial vestibular nuclei. The synaptic plasticity phenomena taking place at the level of vestibular nuclei could be useful for adapting and consolidating the efficacy of vestibular neuron responsiveness to environmental requirements, as during visuo-vestibular recalibration and vestibular compensation. Following a general introduction on the most salient features of vestibular compensation and visuo-vestibular adaptation, which are two plastic events involving neuronal circuitry within the medial vestibular nuclei, the second and third sections describe the results from rat brainstem slice studies, demonstrating the possibility to induce long-term potentiation and depression in the medial vestibular nuclei, following high frequency stimulation of the primary vestibular afferents. In particular the mechanisms sustaining the induction and expression of vestibular long-term potentiation and depression, such as the role of various glutamate receptors and retrograde messengers have been described. The relevant role of the interaction between the platelet-activating factor, acting as a retrograde messenger, and the presynaptic metabotropic glutamate receptors, in determining the full expression of vestibular long-term potentiation is also underlined. In addition, the mechanisms involved in vestibular long-term potentiation have been compared with those leading to long-term potentiation in the hippocampus to emphasize the most significant differences emerging from vestibular studies. The fourth part, describes recent results demonstrating the essential role of nitric oxide, another retrograde messenger, in the induction of vestibular potentiation. Finally the fifth part suggests the possible functional significance of different action times of the two retrograde messengers and metabotropic glutamate receptors, which are involved in mediating the presynaptic mechanism sustaining vestibular long-term potentiation.

Afferent Pathways↗
PubMed2006

Possible sources and sites of action of the nitric oxide involved in synaptic plasticity at spinal lamina I projection neurons.

The synaptic long-term potentiation between primary afferent C-fibers and spinal lamina I projection neurons is a cellular model for hyperalgesia [Ikeda H, Heinke B, Ruscheweyh R, Sandkühler J (2003) Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science 299:1237-1240]. In lamina I neurons with a projection to the periaqueductal gray, this long-term potentiation is dependent on nitric oxide. In the present study, we used immunohistochemistry to detect possible sources and sites of action of the nitric oxide necessary for the long-term potentiation at lamina I spino-periaqueductal gray neurons in rats. None of the three isoforms of the nitric oxide synthase was expressed in a significant number of lamina I spino-periaqueductal gray neurons or primary afferent C-fibers (as evaluated by staining of their cell bodies in the dorsal root ganglia). However, endothelial and inducible nitric oxide synthase were found throughout the spinal cord vasculature and neuronal nitric oxide synthase was present in a number of neurons in laminae II and III. The nitric oxide target soluble guanylyl cyclase was detected in most lamina I spino-periaqueductal gray neurons and in approximately 12% of the dorsal root ganglion neurons, all of them nociceptive as evaluated by coexpression of substance P. Synthesis of cyclic 3',5'-guanosine monophosphate upon stimulation by a nitric oxide donor confirmed the presence of active guanylyl cyclase in at least a portion of the spino-periaqueductal gray neuronal cell bodies. We therefore propose that nitric oxide generated in neighboring neurons or blood vessels acts on the spino-periaqueductal gray neuron and/or the primary afferent C-fiber to enable long-term potentiation. Lamina I spino-parabrachial neurons were stained for comparison and yielded similar results.

Animals↗
PubMed2004

Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors.

To address the role of D1 receptors in the medial prefrontal cortex, we combined pharmacological and genetic manipulations to examine long-term synaptic potentiation (LTP)/long-term synaptic depression (LTD) in brain slices of rats and mice. We found that the D1 antagonist SCH23390 selectively blocked the maintenance but not the induction of LTP in the prefrontal cortex. Conversely, activation of D1 receptors facilitated the maintenance of LTP, and this effect is impaired in heterozygous D1 receptor knockout mice. Low-frequency stimulation induced a transient depression in the medial prefrontal cortex. This depression could be transformed into LTD by coapplication of dopamine. Coapplication of dopamine, however, shows no facilitating effect on LTD in heterozygous D1 receptor knockout mice. These results provide pharmacological and genetic evidence for a role of D1 receptors in the bidirectional modulation of synaptic plasticity in the medial prefrontal cortex. The absence of this modulation in heterozygous knockout mice shows that a dysregulation of dopamine receptor expression levels can have dramatic effects on synaptic plasticity in the prefrontal cortex.

Animals↗