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Journal ArticleDOI

LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite

25 Nov 1999-Nature (Nature Publishing Group)-Vol. 402, Iss: 6760, pp 421-425
TL;DR: In this paper, the morphology of synapses activated by high-frequency stimulation and identified by accumulated calcium in dendritic spines was analyzed using electron microscopy to identify the formation of new synapses contacting the same presynaptic terminal.
Abstract: Structural remodelling of synapses and formation of new synaptic contacts has been postulated as a possible mechanism underlying the late phase of long-term potentiation (LTP), a form of plasticity which is involved in learning and memory Here we use electron microscopy to analyse the morphology of synapses activated by high-frequency stimulation and identified by accumulated calcium in dendritic spines LTP induction resulted in a sequence of morphological changes consisting of a transient remodelling of the postsynaptic membrane followed by a marked increase in the proportion of axon terminals contacting two or more dendritic spines Three-dimensional reconstruction revealed that these spines arose from the same dendrite As pharmacological blockade of LTP prevented these morphological changes, we conclude that LTP is associated with the formation of new, mature and probably functional synapses contacting the same presynaptic terminal and thereby duplicating activated synapses
Citations
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Journal ArticleDOI
19 Dec 2002-Nature
TL;DR: The measurements suggest that sensory experience drives the formation and elimination of synapses and that these changes might underlie adaptive remodelling of neural circuits.
Abstract: Do new synapses form in the adult cortex to support experience-dependent plasticity? To address this question, we repeatedly imaged individual pyramidal neurons in the mouse barrel cortex over periods of weeks. We found that, although dendritic structure is stable, some spines appear and disappear. Spine lifetimes vary greatly: stable spines, about 50% of the population, persist for at least a month, whereas the remainder are present for a few days or less. Serial-section electron microscopy of imaged dendritic segments revealed retrospectively that spine sprouting and retraction are associated with synapse formation and elimination. Experience-dependent plasticity of cortical receptive fields was accompanied by increased synapse turnover. Our measurements suggest that sensory experience drives the formation and elimination of synapses and that these changes might underlie adaptive remodelling of neural circuits.

1,867 citations

Journal ArticleDOI
TL;DR: By this account, neurotrophins may participate in activity-dependent synaptic plasticity, linking synaptic activity with long-term functional and structural modification of synaptic connections.
Abstract: The role of neurotrophins as regulatory factors that mediate the differentiation and survival of neurons has been well described. More recent evidence indicates that neurotrophins may also act as synaptic modulators. Here, I review the evidence that synaptic activity regulates the synthesis, secretion and action of neurotrophins, which can in turn induce immediate changes in synaptic efficacy and morphology. By this account, neurotrophins may participate in activity-dependent synaptic plasticity, linking synaptic activity with long-term functional and structural modification of synaptic connections.

1,783 citations

Journal ArticleDOI
TL;DR: Recent evidence for structural forms of synaptic plasticity in the mammalian cortex involves cell type-specific structural plasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively.
Abstract: Synaptic plasticity in adult neural circuits may involve the strengthening or weakening of existing synapses as well as structural plasticity, including synapse formation and elimination. Indeed, long-term in vivo imaging studies are beginning to reveal the structural dynamics of neocortical neurons in the normal and injured adult brain. Although the overall cell-specific morphology of axons and dendrites, as well as of a subpopulation of small synaptic structures, are remarkably stable, there is increasing evidence that experience-dependent plasticity of specific circuits in the somatosensory and visual cortex involves cell type-specific structural plasticity: some boutons and dendritic spines appear and disappear, accompanied by synapse formation and elimination, respectively. This Review focuses on recent evidence for such structural forms of synaptic plasticity in the mammalian cortex and outlines open questions.

1,696 citations

Journal ArticleDOI
TL;DR: This work has reported the involvement of a 'parallel' but distinct kinase cascade leading to the activation of p38 MAPK, which might control distinct forms of synaptic plasticity in the adult brain.
Abstract: The mitogen-activated protein kinase (MAPK) cascade that leads to the activation of extracellular signal-regulated kinases-1 and -2 (ERK1 and ERK2) has a key role in the differentiation of some cell types and the proliferation of others. However, several recent reports implicate this cascade in the control of synaptic plasticity in the adult brain. ERK signalling seems to be essential for characterized neuronal transcriptional events, and might also regulate synaptic targets to control plasticity. Another recently emerging story is the involvement of a 'parallel' but distinct kinase cascade leading to the activation of p38 MAPK, which might control distinct forms of synaptic plasticity.

1,396 citations


Cites background from "LTP promotes formation of multiple ..."

  • ...This cytoskeletal remodelling, often termed structural plasticity, is also induced by stimuli that can lead to LT...

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Journal ArticleDOI
TL;DR: There is no evidence that changes in the morphology of spines after LTP are necessary or sufficient for the induction or maintenance of LTP, but a strong correlation between synaptic plasticity and morphological changes in spines is shown.
Abstract: Dendritic spines are morphological specializations that receive synaptic inputs and compartmentalize calcium. In spite of a long history of research, the specific function of spines is still not well understood. Here we review the current status of the relation between morphological changes in spines and synaptic plasticity. Since Cajal and Tanzi proposed that changes in the structure of the brain might occur as a consequence of experience, the search for the morphological correlates of learning has constituted one of the central questions in neuroscience. Although there are scores of studies that encompass this wide field in many species, in this review we focus on experimental work that has analyzed the morphological consequences of hippocampal long-term potentiation (LTP) in rodents. Over the past two decades many studies have demonstrated changes in the morphology of spines after LTP, such as enlargements of the spine head and shortenings of the spine neck. Biophysically, these changes translate into an increase in the synaptic current injected at the spine, as well as shortening of the time constant for calcium compartmentalization. In addition, recent online studies using time-lapse imaging have reported increased spinogenesis. The currently available data show a strong correlation between synaptic plasticity and morphological changes in spines, although at the same time, there is no evidence that these morphological changes are necessary or sufficient for the induction or maintenance of LTP. Still, they highlight once more how form and function go hand in hand in the central nervous system.

1,243 citations


Cites background from "LTP promotes formation of multiple ..."

  • ...Bifurcating spines (Trommald et al 1990) and ultimately even closely associated pairs of spines emanating from one dendrite and touching the same presynaptic element occur (Toni et al 1999)....

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  • ...Toni et al (1999) then scrutinized these spines for morphological changes and found that in many cases after stimulation there were pairs or triplets of (calcium precipitate– marked) spines making contact with the same presynaptic terminal....

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  • ...This study (Toni et al 1999) was an extension of earlier work from the same laboratory (Buchs & Muller 1996) using a technique to select for the stimulated synapses and therefore the location in which morphological changes were expected to occur....

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  • ...It also is worthwhile to emphasize that although the correlation between LTP and some morphological events such as spinogenesis is well documented (Engert & Bonhoeffer 1999, Toni et al 1999), it is important to take it as such: correlation not necessarily proving causality....

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  • ...Synapses that were already large break apart, forming perforated synapses (Peters & Kaiserman-Abramof 1969, Toni et al 1999)....

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References
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Journal ArticleDOI
07 Jan 1993-Nature
TL;DR: The best understood form of long-term potentiation is induced by the activation of the N-methyl-d-aspartate receptor complex, which allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and post Synaptic mechanisms to generate a persistent increase in synaptic strength.
Abstract: Long-term potentiation of synaptic transmission in the hippocampus is the primary experimental model for investigating the synaptic basis of learning and memory in vertebrates. The best understood form of long-term potentiation is induced by the activation of the N-methyl-D-aspartate receptor complex. This subtype of glutamate receptor endows long-term potentiation with Hebbian characteristics, and allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and postsynaptic mechanisms to generate a persistent increase in synaptic strength.

11,123 citations


"LTP promotes formation of multiple ..." refers background in this paper

  • ...has been postulated as a possible mechanism underlying the late phase of long-term potentiation (LTP), a form of plasticity which is involved in learning and memor...

    [...]

Journal ArticleDOI
24 Oct 1997-Science
TL;DR: DNA microarrays containing virtually every gene of Saccharomyces cerevisiae were used to carry out a comprehensive investigation of the temporal program of gene expression accompanying the metabolic shift from fermentation to respiration, and the expression patterns of many previously uncharacterized genes provided clues to their possible functions.
Abstract: DNA microarrays containing virtually every gene of Saccharomyces cerevisiae were used to carry out a comprehensive investigation of the temporal program of gene expression accompanying the metabolic shift from fermentation to respiration. The expression profiles observed for genes with known metabolic functions pointed to features of the metabolic reprogramming that occur during the diauxic shift, and the expression patterns of many previously uncharacterized genes provided clues to their possible functions. The same DNA microarrays were also used to identify genes whose expression was affected by deletion of the transcriptional co-repressor TUP1 or overexpression of the transcriptional activator YAP1. These results demonstrate the feasibility and utility of this approach to genomewide exploration of gene expression patterns.

4,792 citations

Journal ArticleDOI
TL;DR: Hippocampal slices prepared from 2-23-day-old neonates were maintained in culture at the interface between air and a culture medium and yielded thin slices which remain 1-4 cell layers thick and are characterized by a well preserved organotypic organization.

3,086 citations


"LTP promotes formation of multiple ..." refers methods in this paper

  • ...Methods Culture preparation and stimulation Experiments were performed on hippocampal organotypic cultures prepared as describe...

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Journal ArticleDOI
TL;DR: A three‐dimensional counting rule and its integral test system, the disector, for obtaining unbiased estimates of the number of arbitrary particles in a specimen is presented.
Abstract: A three-dimensional counting rule and its integral test system, the disector, for obtaining unbiased estimates of the number of arbitrary particles in a specimen is presented. Used in combination with ordinary and recently developed stereological methods unbiased estimates of various mean particle sizes and the variance of particle volume are obtainable on sets of two parallel sections with a known separation. The same principle allows the unbiased estimation of the distribution of individual particle volumes in sets of serial sections.

2,474 citations


"LTP promotes formation of multiple ..." refers methods in this paper

  • ...For the stereological part of the study, the dissector procedure was carried out as describe...

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PatentDOI
27 May 2003-Cell
TL;DR: The results reveal an unanticipated level of regulation which is superimposed on that due to gene-specific transcription factors, a novel mechanism for coordinate regulation of specific sets of genes when cells encounter limiting nutrients, and evidence that the ultimate targets of signal transduction pathways can be identified within the initiation apparatus.

1,963 citations

Trending Questions (1)
How does aberrant neuronal morphology affect the mechanisms underlying LTP?

The provided paper does not discuss the effects of aberrant neuronal morphology on the mechanisms underlying LTP.