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At least 19 recordsLinked to original sources
PubMed1990

Developmental sex differences and effect of ovariectomy on the number of cortical pyramidal cell dendritic spines.

Dendritic spines in the apical shafts of layer V pyramidal neurons were quantitatively assessed in Golgi preparations of visual cortex from male and female rats, 10-60 postnatal days old. The number of dendritic spines increased in both sexes from days 10 to 20. However, we found that 10-day-old females had a significantly greater number of dendritic spines than males of the same age. The absolute difference further increased with increasing age, reaching a maximum at 20 days. Then, the number of dendritic spines progressively decreased in females between days 20 and 60, showing a certain tendency to increase in males during the same period. As a result of this different developmental trend, the number of spines was similar in 60-day-old male and female rats. Ovariectomy of females, at day 30, prevented the decrease in the number of dendritic spines. These results indicate that spine development in the rat visual cortex is dependent on sex, suggesting a possible influence of sex steroids on pyramidal cell maturation.

Aging↗
PubMed1997

Spinophilin, a novel protein phosphatase 1 binding protein localized to dendritic spines.

Dendritic spines receive the vast majority of excitatory synaptic contacts in the mammalian brain and are presumed to contain machinery for the integration of various signal transduction pathways. Protein phosphatase 1 (PP1) is greatly enriched in dendritic spines and has been implicated in both the regulation of ionic conductances and long-term synaptic plasticity. The molecular mechanism whereby PP1 is localized to spines is unknown. We have now characterized a novel protein that forms a complex with the catalytic subunit of PP1 and is a potent modulator of PP1 enzymatic activity in vitro. Within the brain this protein displays a remarkably distinct localization to the heads of dendritic spines and has therefore been named spinophilin. Spinophilin has the properties expected of a scaffolding protein localized to the cell membrane and contains a single consensus sequence in PSD95/DLG/zo-1, which implies cross-linking of PP1 to transmembrane protein complexes. We propose that spinophilin represents a novel targeting subunit for PP1, which directs the enzyme to those substrates in the dendritic spine compartment, e.g., neurotransmitter receptors, which mediate the regulation of synaptic function by PP1.

Amino Acid Sequence↗
PubMed1998

Rapid actin-based plasticity in dendritic spines.

Dendritic spines have been proposed as primary sites of synaptic plasticity in the brain. Consistent with this hypothesis, spines contain high concentrations of actin, suggesting that they might be motile. To investigate this possibility, we made video recordings from hippocampal neurons expressing actin tagged with green fluorescent protein (GFP-actin). This reagent incorporates into actin-containing structures and allows the visualization of actin dynamics in living neurons. In mature neurons, recordings of GFP fluorescence revealed large actin-dependent changes in dendritic spine shape, similar to those inferred from previous studies using fixed tissues. Visible changes occurred within seconds, suggesting that anatomical plasticity at synapses can be extremely rapid. As well as providing a molecular basis for structural plasticity, the presence of motile actin in dendritic spines implicates the postsynaptic element as a primary site of this phenomenon.

Actins↗
PubMed2002

Dendritic spine and dendritic field characteristics of layer V pyramidal neurons in the visual cortex of fragile-X knockout mice.

Fragile-X syndrome is a common form of mental retardation resulting from the inability to produce the fragile-X mental retardation protein. The specific function of this protein is unknown; however, it has been proposed to play a role in developmental synaptic plasticity. Examination of human brain autopsy material has shown that fragile-X patients exhibit abnormalities in dendritic spine structure and number, suggesting a failure of normal developmental dendritic spine maturation and pruning in this syndrome. Similar results using a knockout mouse model have previously been described; however, it was noted in retrospect that the mice used in that study may have carried a mutation for retinal degeneration, which may have affected cell morphology in the visual cortex of those animals. In this study, dendritic spines on layer V pyramidal cells of visual cortices, taken from fragile-X knockout and wild-type control mice without the retinal degeneration mutation and stained using the Golgi-Cox method, were investigated for comparison with the human condition. Quantitative analyses of the lengths, morphologies, and numbers of dendritic spines, as well as amount of dendritic arbor and dendritic branching complexity, were conducted. The fragile-X mice exhibited significantly more long dendritic spines and significantly fewer short dendritic spines than control mice. Similarly, fragile-X mice exhibited significantly more dendritic spines with an immature-like morphology and significantly fewer with a more mature type morphology. However, unlike the human condition, fragile-X mice did not exhibit statistically significant dendritic spine density differences from controls. Fragile-X mice also did not demonstrate any significant differences from controls in dendritic tree complexity or dendritic arbor. Long dendritic spines with immature morphologies are characteristic of early development or a lack of sensory experience. These results are similar to those found in the human condition and further support a role for the fragile-X mental retardation protein specifically in normal dendritic spine developmental processes. They also support the validity of these mice as a model of fragile-X syndrome.

Animals↗
PubMed2005

Dynamics and pathology of dendritic spines.

Dendritic spines are key players in information processing in the brain. Changes in spine shape and wholesale spine turnover provide mechanisms for modifying existing synaptic connections and altering neuronal connectivity. Although neuronal cell death in acute and chronic neurodegenerative diseases is clearly an important factor in decline of cognitive or motor function, loss of dendritic spines, in the absence of cell death, may also contribute to impaired brain function in these diseases, as well as in psychiatric disorders and aging. Because spines can function in neuroprotection in vitro, advances toward a molecular understanding of spine maintenance might one day aid in the design of therapies to minimize neurological damage following excitotoxic injury. In addition, progress in defining the biochemical basis of spine development and stabilization may yield insights into mental retardation and psychiatric disorders.

Animals↗
PubMed2004

Influx of extracellular calcium regulates actin-dependent morphological plasticity in dendritic spines.

Dendritic spines contain a specialized cytoskeleton composed of dynamic actin filaments capable of producing rapid changes in their motility and morphology. Transient changes in Ca2+ levels in the spine cytoplasm have been associated with the modulation of these effects in a variety of ways. To characterize the contribution of Ca2+ fluxes originating through different pathways to these phenomena, we used time-lapse imaging of cultured hippocampal neurons expressing GFP-actin to follow the influence of postsynaptic neurotransmitter receptors, voltage-activated Ca2+ channels and release from internal Ca2+ stores on spine actin dynamics. Stimulation of AMPA receptors produced a rapid blockade of actin-dependent spine motility that was immediately reversible when AMPA was removed. Stimulation of NMDA receptors also blocked spine motility but in this case suppression of actin dynamics was delayed by up to 30 min depending on NMDA concentration and motility was never seen to recover when NMDA was removed. These effects could be mimicked by depolarizing neurons under appropriate circumstances demonstrating the involvement of voltage-activated Ca2+ channels in AMPA receptor-mediated effects and the receptor associated Ca2+ channel in the effects of NMDA. Caffeine, an agent that releases Ca2+ from internal stores, had no immediate effect on spine actin, a result compatible with the lack of caffeine-releasable Ca2+ in cultured hippocampal neurons under resting conditions. Blocking internal store function by thapsigargin led to a delayed suppression of spine actin dynamics that was dependent on extracellular Ca2+. Together these results indicate the common involvement of changes in Ca2+ levels in modulating actin-dependent effects on dendritic spine motility and morphology through several modes of electrophysiological activation.

Actins↗
PubMed2001

On the function of dendritic spines.

Dendritic spines occupy a strategic position in the central nervous system, yet their function is still under debate. Over the past decades, many hypotheses have been put forward to explain the specific function of spines. Recently, imaging experiments have demonstrated that spines compartmentalize calcium, a role that appears necessary for input-specific forms of synaptic plasticity. In addition, it has been discovered that spine morphology is plastic over fast time scales and can be controlled by specific biochemical pathways. Also, several aspects of the spine's morphology appear to be intricately linked to its function. The authors review these recent data and incorporate them into a model for the function of dendritic spines in CNS circuits. In their proposal, spines serve to specifically connect sparse inputs and therefore minimize the wiring necessary in the CNS while maximizing connectivity. By virtue of the same design, spines isolate inputs and thus implement local learning rules. These rules appear only necessary with sparse inputs so these two functions are intimately related. Spines therefore would play a crucial circuit role, remarkably analogous to synaptic matrix elements of associative neural networks. This model highlights the economical, yet elegant, design of CNS circuits.

Animals↗
PubMed2003

Structure and molecular organization of dendritic spines.

Dendritic spines mediate most excitatory synapses in the CNS and are therefore likely to be of major importance for neural processing. We review the structural aspects of dendritic spines, with particular emphasis on recent advances in the characterization of their molecular components. Spine morphology is very diverse and spine size is correlated with the strength of the synaptic transmission. In addition, the spine neck biochemically isolates individual synapses. Therefore, spine morphology directly reflects its function. A large number of molecules have been described in spines, involving several biochemical families. Considering the small size of a spine, the variety of molecules found is astounding, suggesting that spines are paramount examples of biological nanotechnology. Single-molecular studies appear necessary for future progress. The purpose of this rich molecular diversity is still mysterious but endows synapses with a diverse and flexible biochemical machinery.

Actins↗
PubMed2002

Use-dependent inhibition of dendritic spines.

Dendritic spines are now known to be subject to use-dependent plasticity that affects both their structure and their numbers. Recently, it has been demonstrated that a use-dependent increase in the density of dendritic spines occurs in both excitatory and inhibitory synapses in the mouse barrel cortex. Furthermore, it has been shown that although this increase in the density of spines and excitatory synapses is transient, the increase in spinous inhibitory synapses is long-lasting. These findings lend further support to the hypothesis that synapses in the mature cortex are subject to continual use-dependent plasticity.

Animals↗
PubMed2000

Synbindin, A novel syndecan-2-binding protein in neuronal dendritic spines.

Dendritic spines are small protrusions on the surface of dendrites that receive the vast majority of excitatory synapses. We previously showed that the cell-surface heparan sulfate proteoglycan syndecan-2 induces spine formation upon transfection into hippocampal neurons. This effect requires the COOH-terminal EFYA sequence of syndecan-2, suggesting that cytoplasmic molecules interacting with this sequence play a critical role in spine morphogenesis. Here, we report a novel protein that binds to the EFYA motif of syndecan-2. This protein, named synbindin, is expressed by neurons in a pattern similar to that of syndecan-2, and colocalizes with syndecan-2 in the spines of cultured hippocampal neurons. In transfected hippocampal neurons, synbindin undergoes syndecan-2-dependent clustering. Synbindin is structurally related to yeast proteins known to be involved in vesicle transport. Immunoelectron microscopy localized synbindin on postsynaptic membranes and intracellular vesicles within dendrites, suggesting a role in postsynaptic membrane trafficking. Synbindin coimmunoprecipitates with syndecan-2 from synaptic membrane fractions. Our results show that synbindin is a physiological syndecan-2 ligand on dendritic spines. We suggest that syndecan-2 induces spine formation by recruiting intracellular vesicles toward postsynaptic sites through the interaction with synbindin.

Amino Acid Motifs↗
PubMed2006

Imaging membrane potential in dendritic spines.

Dendritic spines mediate most excitatory inputs in the brain. Although it is clear that spines compartmentalize calcium, it is still unknown what role, if any, they play in integrating synaptic inputs. To investigate the electrical function of spines directly, we used second harmonic generation (SHG) imaging of membrane potential in pyramidal neurons from hippocampal cultures and neocortical brain slices. With FM 4-64 as an intracellular SHG chromophore, we imaged membrane potential in the soma, dendritic branches, and spines. The SHG response to voltage was linear and seemed based on an electro-optic mechanism. The SHG sensitivity of the chromophore in spines was similar to that of the parent dendritic shaft and the soma. Backpropagation of somatic action potentials generated SHG signals at spines with similar amplitude and kinetics to somatic ones. Our optical measurements of membrane potential from spines demonstrate directly that backpropagating action potentials invade the spines.

Action Potentials↗
PubMed2001

Ca(2+) signaling in dendritic spines.

Dendritic spines are cellular microcompartments that are isolated from their parent dendrites and neighboring spines. Recently, imaging studies of spine Ca(2+) dynamics have revealed that Ca(2+) can enter spines through voltage-sensitive and ligand-activated channels, as well as through Ca(2+) release from intracellular stores. Relationships between spine Ca(2+) signals and induction of various forms of synaptic plasticity are beginning to be elucidated. Measurements of spine Ca(2+) concentration are also being used to probe the properties of single synapses and even individual calcium channels in their native environment.

Action Potentials↗
PubMed1999

Structure, development, and plasticity of dendritic spines.

Dendritic spines are distinguished by their shapes, subcellular composition, and synaptic receptor subtypes. Recent studies show that actin-dependent movements take place in spine heads, that spines emerge from stubby and shaft synapses after dendritic filopodia disappear, and that spines can form without synaptic activation, are maintained by optimal activation, and are lost with excessive activation or during degeneration.

Animals↗
PubMed1997

Isoform specificity in the relationship of actin to dendritic spines.

Dendritic spines contain high concentrations of actin, but neither the isoforms involved nor the mechanism of accumulation is known. In situ hybridization with specific probes established that beta- and gamma-cytoplasmic actins are selectively expressed at high levels by spine-bearing neurons. Transfecting cultured hippocampal neurons with epitope-tagged actin isoforms showed that cytoplasmic beta- and gamma-cytoplasmic actins are correctly targeted to spines, whereas alpha-cardiac muscle actin, which is normally absent from neurons, formed aggregates in dendrites. The transfected actin cDNAs contained only coding domains, suggesting that spine targeting involves amino acid sequences in the proteins, an interpretation supported by experiments with chimeric cDNAs in which C-terminal actin sequences were found to be determinative in spine targeting. By contrast to actin, microtubule components, including tubulin and MAP2, were restricted to the dendritic shaft domain. The close association of cytoplasmic actins with spines together with their general involvement in cell surface motility further supports the idea that actin motility-based changes in spine shape may contribute to synaptic plasticity.

Actins↗
PubMed2004

On the electrical function of dendritic spines.

Dendritic spines mediate most excitatory inputs in the brain, yet their function is still unclear. Imaging experiments have demonstrated their role in biochemical compartmentalization at individual synapses, yet theoretical studies have suggested that they could serve an electrical function in transforming synaptic inputs and transmitting dendritic spikes. Recent data indicate that spines possess voltage-dependent conductances and that these channels can be spine-specific. Although direct experimental investigations of the electrical properties of spines have not yet taken place, spines could play a significant electrical role, greatly influencing dendritic integration and the function of neural circuits.

Animals↗
PubMed2000

From form to function: calcium compartmentalization in dendritic spines.

Dendritic spines compartmentalize calcium, and this could be their main function. We review experimental work on spine calcium dynamics. Calcium influx into spines is mediated by calcium channels and by NMDA and AMPA receptors and is followed by fast diffusional equilibration within the spine head. Calcium decay kinetics are controlled by slower diffusion through the spine neck and by spine calcium pumps. Calcium release occurs in spines, although its role is controversial. Finally, the endogenous calcium buffers in spines remain unknown. Thus, spines are calcium compartments because of their morphologies and local influx and extrusion mechanisms. These studies highlight the richness and heterogeneity of pathways that regulate calcium accumulations in spines and the close relationship between the morphology and function of the spine.

Animals↗
PubMed2004

Structural basis of long-term potentiation in single dendritic spines.

Dendritic spines of pyramidal neurons in the cerebral cortex undergo activity-dependent structural remodelling that has been proposed to be a cellular basis of learning and memory. How structural remodelling supports synaptic plasticity, such as long-term potentiation, and whether such plasticity is input-specific at the level of the individual spine has remained unknown. We investigated the structural basis of long-term potentiation using two-photon photolysis of caged glutamate at single spines of hippocampal CA1 pyramidal neurons. Here we show that repetitive quantum-like photorelease (uncaging) of glutamate induces a rapid and selective enlargement of stimulated spines that is transient in large mushroom spines but persistent in small spines. Spine enlargement is associated with an increase in AMPA-receptor-mediated currents at the stimulated synapse and is dependent on NMDA receptors, calmodulin and actin polymerization. Long-lasting spine enlargement also requires Ca2+/calmodulin-dependent protein kinase II. Our results thus indicate that spines individually follow Hebb's postulate for learning. They further suggest that small spines are preferential sites for long-term potentiation induction, whereas large spines might represent physical traces of long-term memory.

Actins↗
PubMed2000

Glutamate receptors regulate actin-based plasticity in dendritic spines.

Dendritic spines at excitatory synapses undergo rapid, actin-dependent shape changes which may contribute to plasticity in brain circuits. Here we show that actin dynamics in spines are potently inhibited by activation of either AMPA or NMDA subtype glutamate receptors. Activation of either receptor type inhibited actin-based protrusive activity from the spine head. This blockade of motility caused spines to round up so that spine morphology became both more stable and more regular. Inhibition of spine motility by AMPA receptors was dependent on postsynaptic membrane depolarization and influx of Ca 2+ through voltage-activated channels. In combination with previous studies, our results suggest a two-step process in which spines initially formed in response to NMDA receptor activation are subsequently stabilized by AMPA receptors.

Actins↗