Dendritic spine formation and pruning: common cellular mechanisms?

Segal, Menahem; Korkotian, Eduard; Murphy, Diane D.

doi:10.1016/s0166-2236(99)01499-x

Cited by 173 publications

(127 citation statements)

References 50 publications

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“…Our data further suggest that the expression of glutamate receptors must be independently controlled at individual spines. Given that each spine receives only one synaptic input 13 , our data indicate the highest possible degree of freedom is available in synaptic connections in the dendrites, which has been assumed in the learning models of most neural network theories 17 .The relationship between spine geometry and expression of functional AMPA receptors demonstrated here provides substantial support to the hypothesis that neuronal fine structures have functional correlates in the brain 13,18,21 . It has recently been suggested that electrical activity controls the size and number of spines 21,22,[39][40][41][42] , and that the expression of glutamate receptors is tightly regulated by abundant cytoskeletal structures present in spines [3][4][5] .…”

supporting

confidence: 55%

“…It has recently been suggested that electrical activity controls the size and number of spines 21,22,[39][40][41][42] , and that the expression of glutamate receptors is tightly regulated by abundant cytoskeletal structures present in spines [3][4][5] . One can therefore surmise that spine structures are a key determinant of synaptic efficacy via control of the distribution of the AMPA receptors 9,10,43 .…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the Hebbian principle of learning as well as most theories of neuronal networks assume that the strength of synaptic connections is subject to independent control 17 . Moreover, spine geometry has been proposed to be a key determinant of synaptic function and memory in the brain 13,14,[18][19][20][21][22] .…”

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Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

et al. 2001

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Dendritic spines serve as preferential sites of excitatory synaptic connections and are pleomorphic. To address the structure-function relationship of the dendritic spines, we used two-photon uncaging of glutamate to allow mapping of functional glutamate receptors at the level of the single synapse. Our analyses of the spines of CA1 pyramidal neurons reveal that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors are abundant (up to 150/ spine) in mushroom spines but sparsely distributed in thin spines and filopodia. The latter may be serving as the structural substrates of the silent synapses that have been proposed to play roles in development and plasticity of synaptic transmission. Our data indicate that distribution of functional AMPA receptors is tightly correlated with spine geometry and that receptor activity is independently regulated at the level of single spines.Most excitatory synaptic transmission in the mammalian central nervous system relies on glutamate as a neurotransmitter, and postsynaptic glutamate receptors are central in both the acquisition and maintenance of memory 1, 2 . Substantial biochemical evidence indicates that glutamate receptors in postsynaptic densities (PSDs) are regulated by various protein machineries that link the receptors to the cytoskeleton 3,4,5 and that control the insertion [6][7][8][9][10] and phosphorylation of the receptors 11,12 . Individual dendritic spines have been thought to act as functional compartments of glutamate receptor expression, given that they are physically and thus metabolically separated from the body of the dendrite by the narrow spine neck [13][14][15][16] . Indeed, the Hebbian principle of learning as well as most theories of neuronal networks assume that the strength of synaptic connections is subject to independent control 17 . Moreover, spine geometry has been proposed to be a key determinant of synaptic function and memory in the brain 13, 14, 18-22 . Correspondence to: Haruo Kasai. These various hypotheses have not been tested experimentally, however, because it is not possible to systematically investigate postsynaptic glutamate sensitivities at the level of the individual spine by classical electrophysiological approaches 16,23 . Also, the number of functional AMPA-sensitive glutamate receptors in individual spines has not been estimated directly. Two-photon excitation of caged-glutamate compounds may overcome these difficulties 24 as a result of the inherent three-dimensional resolution of neurotransmitter application associated with this technique. However, caged-glutamate compounds with a cross-section for two-photon absorption, a rate of photolysis, and a stability in aqueous solution sufficient for such studies have not previously been described [25][26][27] . NIH Public AccessWe developed a caged-glutamate compound and microscopic system for two-photon excitation that allowed systematic investigation of functional glutamate receptors at the level of the individual synapse. Our experiment...

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Section: Discussionmentioning

confidence: 99%

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Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

et al. 2001

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“…However, most of these spines are of the long and thin Type-III, known to be highly motile and unstable structures (Dailey and Smith, 1996;Dunaevsky et al, 1999) and characteristic of immature synapses (Sorra and Harris, 2000). The fact that longer exposures to k-252a by itself caused spine loss (Tyler and PozzoMiller, 2001), suggests that an initial increase in long and thin spines may precede spine regression leading to spine pruning (Segal et al, 2000). Alternatively, these observations may reflect the functional antagonism between p75 NTR and Trk receptor signaling for dendritic spine formation and maintenance.…”

Section: Neurotrophin Signaling Through P75 Ntr Receptorsmentioning

confidence: 99%

Transient receptor potential channels as novel effectors of brain-derived neurotrophic factor signaling: Potential implications for Rett syndrome

Amaral

Chapleau

Pozzo-Miller

2007

Pharmacology & Therapeutics

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In addition to their prominent role as survival signals for neurons in the developing nervous system, neurotrophins have established their significance in the adult brain as well, where their modulation of synaptic transmission and plasticity may participate in associative learning and memory. These crucial activities are primarily the result of neurotrophin regulation of intracellular Ca 2+ homeostasis and, ultimately, changes in gene expression. Outlined in the following review is a synopsis of neurotrophin signaling with a particular focus upon BDNF and its role in hippocampal synaptic plasticity and neuronal Ca 2+ homeostasis. Neurotrophin signaling through Trk and p75 NTR receptors are also discussed, reviewing recent results that indicate signaling through these two receptor modalities leads to opposing cellular outcomes. We also provide an intriguing look into the TRPC family of ion channels as distinctive targets of BDNF signaling; these channels are critical for capacitative Ca 2+ entry, which, in due course, mediates changes in neuronal structure including dendritic spine density. Finally, we expand these topics into an exploration of mental retardation, in particular Rett Syndrome, where dendritic spine abnormalities may underlie cognitive impairments. We propose that understanding the role of neurotrophins in synapse formation, plasticity and maintenance will make fundamental contributions to the development of therapeutic strategies to improve cognitive functions in developmental disorders associated with mental retardation.

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“…The model also includes equations for activity-dependent changes in the calcium concentration in spines as well as changes in spine stem resistance that depend on the level of calcium in an individual spine. The calcium-mediated changes in spine density and spine stem resistance are based on a conceptual model proposed by Segal et al [1] where low calcium concentrations lead to spine shrinkage and pruning, an increase in calcium concentration leads to spine elongation and formation of new spines, and significantly higher values cause spine shrinkage and pruning.We use computational studies to investigate the changes in spine density and structure for differing synaptic inputs and demonstrate the effects of these changes on the inputoutput properties of the dendritic branch. Moderate amounts of high-frequency synaptic activation to dendritic spines cause an increase in spine stem resistance, which is correlated with spine stem elongation.…”

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A model of activity-dependent changes in dendritic spine density and spine structure

Crook

Dur-e-Ahmad

Baer

2007

Mathematical Biosciences and Engineering

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Recent evidence indicates that the morphology and density of dendritic spines are regulated during synaptic plasticity. See for instance a review by [1]. High-frequency stimuli that induce long-term potentiation (LTP) have been associated with increases in the number and size of spines. In contrast, low-frequency stimuli that induce long-term depression (LTD) are associated with decreases in the number and size of spines. Decreases in spine density also occur due to excitotoxicity associated with very high levels of activity such as during seizures.In this work, we extend previous modeling studies [2] by combining a model for activity-dependent spine density with one for calcium-mediated spine stem restructuring. The model is based on the standard dimensionless cable equation for the changes in membrane potential in a passive dendrite. An additional equation characterizes the activity-dependent changes in spine density along the dendrite. For this continuum model, a typical HodgkinHuxley type current balance equation represents the change in membrane potential in an isopotential compartment representing a spine head. Both the cable equation and the current balance equation rely on the spine stem current to represent current flow between the spines and the dendrite. The model also includes equations for activity-dependent changes in the calcium concentration in spines as well as changes in spine stem resistance that depend on the level of calcium in an individual spine. The calcium-mediated changes in spine density and spine stem resistance are based on a conceptual model proposed by Segal et al. [1] where low calcium concentrations lead to spine shrinkage and pruning, an increase in calcium concentration leads to spine elongation and formation of new spines, and significantly higher values cause spine shrinkage and pruning.We use computational studies to investigate the changes in spine density and structure for differing synaptic inputs and demonstrate the effects of these changes on the inputoutput properties of the dendritic branch. Moderate amounts of high-frequency synaptic activation to dendritic spines cause an increase in spine stem resistance, which is correlated with spine stem elongation. In addition, the spine density increases both inside and outside the input region. The model is formulated so that this LTP-inducing stimulus eventually leads to structural stability. In contrast, a prolonged low-frequency stimulation paradigm that would typically induce LTD results in a decrease in stem resistance (correlated with spine shortening) and an eventual decrease in spine density. Verzi DW, Rheuben MB, Baer SM: Impact of time-dependent changes in spine density and spine shape on the input-output properties of a dendritic branch: A computational study. J

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Dendritic spine formation and pruning: common cellular mechanisms?

Cited by 173 publications

References 50 publications

Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

Transient receptor potential channels as novel effectors of brain-derived neurotrophic factor signaling: Potential implications for Rett syndrome

A model of activity-dependent changes in dendritic spine density and spine structure

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