The dendritic spine: a multifunctional integrative unit

Shepherd, Gordon M.

doi:10.1152/jn.1996.75.6.2197

Cited by 215 publications

(140 citation statements)

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“…The function of dendritic spines has been extensively investigated (Shepherd, 1996;Yuste and Bonhoeffer, 2001;Sabatini et al, 2001;Nimchinsky et al, 2002). Regarding their individual geometrical dimensions, recent studies have proposed that spine length in hippocampal pyramidal neurons contributes to spine-dendrite coupling of Ca 2+ signals Korkotian et al, 2004;Majewska et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons

Pozzo-Miller

2006

Brain Research

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BDNF, a member of the neurotrophin family, is emerging as a key modulator of synaptic structure and function in the CNS. Due to the critical role of postsynaptic Ca 2+ signals in dendritic development and synaptic plasticity, we tested whether long-term exposure to BDNF affects Ca 2+ elevations evoked by coincident excitatory postsynaptic potentials (EPSPs) and back-propagating action potentials (bAPs) in spiny dendrites of CA1 pyramidal neurons within hippocampal slice cultures. In control neurons, a train of 5 coincident EPSPs and bAPs evoked Ca 2+ elevations in oblique radial branches of the main apical dendrite that were of similar amplitude than those evoked by a train of 5 bAPs alone. On the other hand, dendritic Ca 2+ signals evoked by coincident EPSPs and bAPs were always larger than those triggered by bAPs in CA1 neurons exposed to BDNF for 48 h. This difference was not observed after blockade of NMDA receptors (NMDARs) with D,L-APV, but only in BDNFtreated neurons, suggesting that Ca 2+ signals in oblique radial dendrites include a synaptic NMDARdependent component. Co-treatment with the receptor tyrosine kinase inhibitor k-252a prevented the effect of BDNF on coincident dendritic Ca 2+ signals, suggesting the involvement of neurotrophin Trk receptors. These results indicate that long-term exposure to BDNF enhances Ca 2+ signaling during coincident pre-and postsynaptic activity in small spiny dendrites of CA1 pyramidal neurons, representing a potential functional consequence of neurotrophin-mediated dendritic remodeling in developing neurons.

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Section: Discussionmentioning

confidence: 99%

BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons

Pozzo-Miller

2006

Brain Research

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“…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.…”

Section: Introductionmentioning

confidence: 99%

“…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 .…”

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confidence: 99%

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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“…It has been hypothesized that alterations in synaptic activity can cause morphologic changes in dendritic spines [27,40,46]. Conversely, morphologic changes in dendritic spines [51,64,83] have profound effects on the electrical and biochemical properties of synapses [17,67], and may regulate the efficacy of synaptic transmission [83].…”

Section: Introductionmentioning

confidence: 99%

Stereologic estimates of total spinophilin-immunoreactive spine number in area 9 and the CA1 field: Relationship with the progression of Alzheimer's disease

Akram

Christoffel

Rocher

et al. 2008

Neurobiology of Aging

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The loss of presynaptic markers is thought to represent a strong pathologic correlate of cognitive decline in Alzheimer's disease (AD). Spinophilin is a postsynaptic marker mainly located to the heads of dendritic spines. We assessed total numbers of spinophilin-immunoreactive puncta in the CA1 and CA3 fields of hippocampus and area 9 in 18 elderly individuals with various degrees of cognitive decline. The decrease in spinophilin-immunoreactivity was significantly related to both Braak neurofibrillary tangle (NFT) staging and clinical severity but not Aβ deposition staging. The total number of spinophilin-immunoreactive puncta in CA1 field and area 9 were significantly related to MMSE scores and predicted 23.5% and 61.9% of its variability. The relationship between total number of spinophilin-immunoreactive puncta in CA1 field and MMSE scores did not persist when adjusting for Braak NFT staging. In contrast, the total number of spinophilin-immunoreactive puncta in area 9 was still significantly related to the cognitive outcome explaining an extra 9.6% of MMSE and 25.6% of the Clinical Dementia Rating scores variability. Our data suggest that neocortical dendritic spine loss is an independent parameter to consider in AD clinicopathologic correlations.

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The dendritic spine: a multifunctional integrative unit

Cited by 215 publications

References 0 publications

BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons

BDNF enhances dendritic Ca2+ signals evoked by coincident EPSPs and back-propagating action potentials in CA1 pyramidal neurons

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

Stereologic estimates of total spinophilin-immunoreactive spine number in area 9 and the CA1 field: Relationship with the progression of Alzheimer's disease

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