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At least 19 recordsLinked to original sources
PubMed1979

Synaptic plasticity.

Synaptic plasticity is manifested by long-lasting changes in synaptic potency. Increased potency is of special importance in relation to the neural basis of memory. Even mild repetitive stimulation evokes large and prolonged potentiations of hippocampal synapses, as is revealed by electrical recording either in vivo or in vitro. More importantly there is a matching hypertrophy of the synaptic spines on the dendrites of hippocampal granule cells, as is shown by most convincing electronmicrographs. The increase is to about 40% some 2 h after a mild stimulation (900 impulses) and there was relatively little decline by 23 h. There is brief reference to the metabolic processes that could be involved in this plastic response.

Animals↗
PubMed1992

[Synaptic plasticity and gene products].

Synaptic plasticity is thought to be the basic mechanism underlying learning and memory. The cellular mechanisms underlying synaptic plasticity have been extensively investigated in invertebrates and in vertebrates. What is the nature of synaptic plasticity? Can genes and gene products regulate plasticity? If so, how? The behavioral sensitization of the gill-and-siphon-withdrawal reflex of Aplysia is a simple model of plasticity in invertebrates, and can be examined in dissociated cell culture. Using a model of plasticity in cell culture, the molecular cascades of both short-term and long-term sensitization have been investigated, and characterized. Both gene transcription and protein synthesis were shown to contribute to the long-term sensitization. Long-term potentiation (LTP) is a well-characterized model for synaptic plasticity in vertebrates. Many possible cascades have been proposed, but it has not yet been settled whether an increase of transmitter release from presynaptic terminal, an increase of synaptic current, is responsible for the maintenance of LTP. Inhibition of protein synthesis resulted in a failure to maintain LTP over 3-4 hours. Thus, new protein synthesis may be needed for the maintenance of LTP. Induction of so-called immediate early genes that are induced immediately upon depolarization or neurotransmitter stimulation of the neuron has been studied as a possible mechanism underlying LTP. However, there is no good evidence yet implicating gene regulation to be involved in plasticity in vertebrates.

Action Potentials↗
PubMedDate not supplied

Contributions of dendritic spines and perforated synapses to synaptic plasticity.

The dynamic nature of synaptic connections has presented morphologists with considerable problems which, from a structural perspective, have frustrated the development of ideas on synaptic plasticity. Gradually, however, progress has been made on concepts such as the structural remodelling and turnover of synapses. This has been considerably helped by the recent elaboration of unbiased stereological procedures. The major emphasis of this review is on naturally occurring synaptic plasticity, which is regarded as an ongoing process in the postdevelopmental CNS. The focus of attention are PSs, with their characteristically discontinuous synaptic active zone, since there is mounting evidence that this synaptic type is indicative of synaptic remodelling and turnover in the mature CNS. Since the majority of CNS synapses can only be considered in terms of their relationship to dendritic spines, the contribution of these spines to synaptic plasticity is discussed initially. Changes in the configuration of these spines appears to be crucial for the plasticity, and these can be viewed in terms of the significance of the cytoskeleton, of various dendritic organelles, and also of the biophysical properties of spines. Of the synaptic characteristics that may play a role in synaptic plasticity, the PSD, synaptic curvature, the spinule, coated vesicles, polyribosomes, and the spine apparatus have all been implicated. Each of these is assessed. Special emphasis is placed on PSs because of their ever-increasing significance in discussions of synaptic plasticity. The possibility of their being artefacts is dismissed on a number of grounds, including consideration of the results of serial section studies. Various roles, other than one in synaptic plasticity have been put forward in discussing PSs. Although relevant to synaptic plasticity, these include a role in increasing synaptic efficacy, as a more permanent type of synaptic connection, or as a route for the intercellular exchange of metabolites or membrane components. The consideration of many estimates of synaptic density, and of PS frequency, have proved misleading, since studies have reported diverse and sometimes low figures. A recent reassessment of PS frequency, using unbiased stereological procedures, has provided evidence that in some brain regions PSs may account for up to 40% of all synapses. All ideas that have been put forward to date regarding the role of PSs are examined, with particular attention being devoted to the major models of Nieto-Sampedro and co-workers.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Astrocytes within the hypothalamic arcuate nucleus contain estrogen-sensitive peroxidase, bind fluorescein-conjugated estradiol, and may mediate synaptic plasticity in the rat.

Estrogen treatment induces synaptic plasticity accompanied by damaged structures and aggregates of peroxidase in astrocytes in the hypothalamic arcuate nucleus of the rat. Synaptic plasticity also occurs within the arcuate nucleus after physiologic surges of estrogen. Although the function of estrogen-induced peroxidase is unclear at present, in other systems peroxidase can generate free radicals by catalyzing the oxidation of some molecules, including estrogen. Because free radicals underlie remodeling in a number of tissues, estrogen-induced free radicals could mediate synaptic remodeling within the arcuate nucleus. Although they contain estrogen-inducible peroxidase, astrocytes do not contain estrogen receptors as measured by conventional techniques, suggesting that estrogen-inducible peroxidase arises from some novel mechanism. Estrogen could induce peroxidase within receptor-deficient astrocytes by binding to receptors in neurons and stimulating the release of some factor that interacts with astrocytes. Alternatively, estrogen could act directly on astrocytes in the absence of estrogen receptors. Although astrocytes in the hypothalamus of the rat do not contain classical nuclear estrogen receptors, they do bind fluorescein-conjugated estradiol in extranuclear sites. The distribution of fluorescein-conjugated estradiol binding within the hypothalamus overlaps that of peroxidase-rich astrocytes, and double labeling reveals many cells with the stellate morphology of astrocytes, containing both peroxidase and fluorescein-conjugated estradiol binding. However, because peroxidase and fluorescein-conjugated estradiol always occupy different compartments of the cell, the fluorescein-conjugated estradiol is not binding to peroxidase.

Animals↗
PubMed1988

Quantitative morphology of synaptic plasticity in the aging brain.

Quantitation of synaptic ultrastructural changes is of great importance in neurobiology, since merely qualitative alterations, if not extreme, are not readily detectable. In the present paper we discuss our previous and present findings on the number (numerical density: Nv), size (average length of the synaptic profiles: L) and surface contact area (surface density: Sv) of the synaptic junctions in aging rodent and human brains. We found that number and size of the synapses are in a close inverse relationship so as to maintain the total surface contact are among the nerve cells constant. These three parameters are closely related to each other, their quantitation may thus represent a reliable index of the morphological aspects of synaptic plasticity, i.e. the modification of ultrastructure occurring at synaptic membranes after transient changes in synaptic activity. During aging, the morphological plasticity of synapses appears to be seriously impaired: the number of synapses and the total surface contact area among the nerve cells are markedly reduced. However, old nerve cells seem to retain the ability to modify their synaptic endings and to partially compensate for the reduced surface density of the contact zones by expanding the average size of the persisting junctions. Our recent studies on synaptic plasticity in human brains from old and demented subjects showed that while the size of the synaptic contacts remains constant, the numerical and surface densities undergo a further decrease in demented brains relative to that in normal aging.

Adult↗
PubMed1992

Synaptic plasticity in Drosophila memory and hyperexcitable mutants: role of cAMP cascade.

Activity-dependent synaptic plasticity has been implicated in the refinement and modification of neural circuits during development and learning. Previous studies show that activity-induced facilitation and potentiation are disrupted at larval neuromuscular junctions in the memory mutants dunce (dnc) and rutabaga (rut) of Drosophila. The diminished learning-memory capacity and synaptic transmission plasticity have been associated with altered cAMP levels since dnc affects the cAMP-specific phosphodiesterase and rut affects adenylate cyclase. In this study, the morphology of larval motor axon terminals was examined by anti-HRP immunohistochemistry. It was found that the numbers of terminal varicosities and branches were increased in dnc mutants, which have elevated cAMP concentrations. Such increase was suppressed in dnc rut double mutants by rut mutations, which reduce cAMP synthesis. More profuse projections of larval motor axons have also been reported in double-mutant combinations of ether à go-go (eag) and Shaker (Sh) alleles, which display greatly enhanced nerve activity as a result of reduction in different K+ currents. Therefore, we examined combinations of dnc and rut with eag and Sh mutations to explore the possible relation between activity- and cAMP-induced morphological changes. We found that the expanded projections in dnc were further enhanced in double mutants of dnc with either eag or Sh, an effect that could again be suppressed by rut. The results provide evidence for altered plasticity of synaptic morphology in memory mutants dnc and rut and suggest a role of cAMP cascade in mediating activity-dependent synaptic plasticity.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

Synaptic plasticity and learning. II: Do different kinds of plasticity underlie different kinds of learning?

This paper discusses certain issues connected with the question of whether synaptic plasticity is involved in information storage by the brain. We begin by contrasting two well documented types of synaptic plasticity--activity-dependent modulation of presynaptic facilitation ("Kandel synapses") and NMDA receptor triggered alterations in excitatory amino acid transmission ("Hebb synapses"). We then propose that, embedded-into appropriate circuitry, these different forms of plasticity might underlie different kinds of learning. In partial support of this idea, we show that, in freely moving rats, intrahippocampal microinfusion of the NMDA-receptor antagonist D,L-AP5 causes a dose-dependent impairment of a type of spatial learning known to be sensitive to disruption by hippocampal lesions (water-maze place-navigation). In a second experiment, the same drug infusion protocol is shown to cause a blockade of hippocampal long-term potentiation in vivo across a comparable dose range. Finally, third, autoradiographic experiments indicate that diffusion of the drug was largely restricted to the hippocampus. Together, these results (1) suggest that blockade of hippocampal NMDA receptors, under conditions which leave baseline synaptic transmission relatively unaffected, blocks a type of learning with which the vertebrate hippocampus has been implicated on the basis of neuropsychological work; and (2) supports Abrams and Kandel's Trends Neurosci. 11 (1988) recent proposal that there may be several logically distinct forms of synaptic plasticity.

Animals↗
PubMed1991

Applicability of the coefficient of variation method for analyzing synaptic plasticity.

The classical coefficient of variation method for "quantal" analysis of synaptic responses allows unambiguous identification of pre- and postsynaptic loci underlying synaptic plasticity only when extensive simplifying restrictions are made. They include invariance of quantal parameters and the assumption that a single afferent produces the evoked potentials or currents. More general theoretical formulations and simulations demonstrate that the standard criteria do not always provide useful guidelines because when the other sources of physiological variance are included, putative pre- and postsynaptic domains may overlap. For example, data typically interpreted as indicating modifications at both sites can be due to a mechanism localized to only one of the two, if parameter variances are taken into consideration in the case of a single input cell, or if there are multiple inputs and the stimulus does not activate all of them reliably. With this perspective, other physiologically realistic hypotheses relevant to the expression of synaptic plasticity, such as that during long-term potentiation, can be envisioned.

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↗
PubMed1992

Synaptic plasticity in the dentate gyrus of aged rats is altered after chronic nimodipine application.

We examined ultrastructural correlates of synaptic plasticity in the hippocampus of young (3 months) vs aged (30 months) Wistar rats and established the effects of the calcium antagonist nimodipine in animals chronically treated from 24 to 30 months. The effects of nimodipine was studied since this compound improves hippocampal neuronal physiology and enhances cognitive function during aging. In the supragranular layer of the dentate gyrus we found a 24% decrease in synaptic density (Nv) in aged animals, while synaptic size (S) was not significantly altered. After nimodipine treatment Nv in aged rats was not significantly different from young adults, thus being significantly increased compared to age-matched controls. The size of synapses was not significantly altered after nimodipine administration. Total synaptic surface area (Sv) in nimodipine-treated animals was significantly increased compared to aged controls, however, Sv remained significantly lower than in young adults. These data indicate that chronic administration of nimodipine enables granular cells in the dentate gyrus to maintain its number of synaptic contacts during the aging process. Furthermore, the presented influence of nimodipine on synaptic plasticity processes may underlie previously reported improved cognitive functioning of aged animals treated similarly with nimodipine.

Aging↗
PubMed1985

A modulating effect of Hygergine on the synaptic plasticity of old rats.

The morphological plasticity of E-PTA stained synaptic junctions was investigated by means of quantitative morphometry in the dentate gyrus supra-granular layer of adult, old and old-Hydergine treated rats. Numerical (Nv) and surface (Sv) density as well as average size of the synapses (S) were the three parameters considered. During aging, Nv and Sv significantly decrease whereas S increases. Hydergine treatment to old rats resulted in a significant increase of Nv and Sv and a significant decrease of S. Present findings are interpreted as a modulating effect of Hydergine on the synaptic plasticity of old rats.

Aging↗
PubMed1986

Synaptic plasticity in vitro: cell culture of identified Aplysia neurons mediating short-term habituation and sensitization.

The gill withdrawal reflex of the marine mollusk, Aplysia californica, shows habituation and sensitization, two simple forms of learning. In order to extend the cellular studies on synaptic plasticity underlying the changes in the reflex behavior, and to explore further the development of synaptic plasticity during synapse formation, we have sought to establish the neural circuit of the gill withdrawal reflex in vitro. We report here the reconstruction of the elementary gill withdrawal circuit in cell culture and find that the cells show short-term homosynaptic depression and heterosynaptic facilitation, the cellular mechanisms of habituation and sensitization, respectively.

Action Potentials↗
PubMed1987

Primary structure and mRNA localization of protein F1, a growth-related protein kinase C substrate associated with synaptic plasticity.

Protein F1 is a neuron-specific, synaptic-enriched, membrane-bound substrate of protein kinase C (PKC) whose phosphorylation is related to synaptic plasticity in the adult. The sequence of 26 N-terminal amino acids was determined from purified rat protein F1. A 78-mer synthetic oligonucleotide designed from the partial N-terminal sequence enabled identification of protein F1 cDNA clones in a rat brain library. F1 protein is a 226 amino acid protein encoded by a 1.5 kb brain-specific, developmentally-regulated mRNA. Transcripts for protein F1 can be detected at birth, and their level declines after maturation. A full-length cDNA clone was transcribed and translated in vitro. Translation products could be immunoprecipitated with anti-F1 antibodies. In situ hybridization analysis revealed protein F1 transcripts in hippocampal pyramidal cells, but not in granule cells. In cerebellum, granule cells contained protein F1 mRNA, while Purkinje cells did not. Co-localization of protein F1 with protein kinase C-II [PKC-II (beta)], rather than PKC-I (gamma) suggests that PKC-II may phosphorylate protein F1.

Amino Acid Sequence↗
PubMed1991

Calcium, network activity, and the role of NMDA channels in synaptic plasticity in vitro.

Functionally effective neuronal circuits are constructed through a competitive process that requires patterned neuronal activity elicited by structured input from the environment. To explore the mechanisms of this activity-dependent synaptic restructuring, we have developed an in vitro preparation of mouse spinal cord neurons maintained in a 3-chambered cell-culture system. Sensory afferents that received chronic electrical stimulation for 3-5 d developed stronger synaptic connections than unstimulated afferents converging onto the same postsynaptic spinal cord neuron. Exposure to 100 microM DL-2-amino-5-phosphonovaleric acid (APV), an antagonist of the NMDA channel, during the stimulation period prevented the competitive advantage associated with electric stimulation. However, when APV was applied with a higher concentration of calcium (3 mM), activity-dependent synaptic plasticity was no longer inhibited by the NMDA receptor antagonist. This reversal of APV block of the plasticity was not impaired by reducing transmitter release with 3 mM magnesium (in addition to 3 mM calcium and APV). A suppressant effect of APV on spontaneous activity was observed, which was attributed to loss of the NMDA component of the EPSP. Activity-dependent plasticity was also blocked if spontaneous activity was suppressed with dilute tetrodotoxin (TTX; 5-10 nM), a dosage that reduces excitability of neurons but is insufficient to block sodium-dependent action potentials. These experiments bring into question how NMDA channel activation is involved in the processes of synaptic remodeling during development. The data suggest that postsynaptic activity is required for synaptic remodeling, but this activity need not involve NMDA receptor activation specifically for activity-evoked synaptic plasticity. Instead, the mechanism for plasticity appears to operate through calcium-dependent processes in general.

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↗
PubMed1991

Altered synaptic plasticity in Drosophila memory mutants with a defective cyclic AMP cascade.

Synaptic transmission was examined in Drosophila mutants deficient in memory function. These mutants, dunce and rutabaga, are defective in different steps of the cyclic adenosine 3',5'-monophosphate (cAMP) cascade. In both dunce and rutabaga larvae, voltage-clamp analysis of neuromuscular transmission revealed impaired synaptic facilitation and post-tetanic potentiation as well as abnormal responses to direct application of dibutyryl cAMP. In addition, the calcium dependence of transmitter release was shifted in dunce. The results suggest that the cAMP cascade plays a role in synaptic facilitation and potentiation and indicate that synaptic plasticity is altered in Drosophila memory mutants.

Action Potentials↗
PubMed1991

Learning-related synaptic plasticity: LTP and LTD.

The past several years have seen studies of synaptic plasticity in both invertebrate and vertebrate nervous systems come of age and lead to important new findings. In particular, current evidence points to a possible presynaptic site for long-term potentiation and the involvement of a retrograde messenger from the postsynaptic neuron. Recent advances in both cerebellar and cortical forms of long-term depression are also discussed.

Animals↗
PubMed1992

K(+)-channel blockers restore synaptic plasticity in the neuromuscular junction of dunce, a Drosophila learning and memory mutant.

The effects of K(+)-channel blockers on synaptic transmission in dunce (dnc), a Drosophila learning and memory mutant, were investigated. Larvae dnc mutants lack facilitation and post-tetanic potentiation (PTP) at their motor end-plates; dnc mutants are also deficient in a form of phosphodiesterase, and exhibit abnormally high levels of cyclic adenosine 3',5'-monophosphate (cAMP). A two-microelectrode voltage-clamp was used to record end-plate currents and spontaneous end-plate currents from longitudinal ventrolateral third-instar larval muscle. The K(+)-channel blockers 3,4-diaminopyridine (3,4-DAP) and tetraethylammonium (TEA), at micromolar concentrations, caused a reversible decrease in end-plate current amplitudes both in wild-type and mutant end-plates. In the presence of blockers, a period of high-frequency stimulation (tetanus) of the nerve gave way to a transient increase in the end-plate currents of dnc mutants resembling facilitation and PTP in normal end-plates; 3,4-DAP and TEA also restored facilitation and PTP in normal end-plates after incubation with a non-hydrolysable analogue of cAMP (8Br-cAMP). It is suggested that a specific K+ conductance might be relevant to the lack of synaptic plasticity at the dnc neuromuscular synapses.

4-Aminopyridine↗