Review
Dendritic spines shaped by synaptic activity

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Abstract

A recent series of exciting observations, using novel high-resolution time-lapse imaging of living cells, has provoked a major shift in our understanding of the dendritic spine, from a stable storage site of long-term memory to a dynamic structure that undergoes rapid morphological variations. Through these recent observations, the molecular mechanisms underlying spine plasticity are beginning to emerge. A common mechanism involving changes in intracellular Ca2+ concentration may control both the formation/elongation and the pruning/retraction of spines. Spine motility may be instrumental in the formation of synapses, may contribute to the anchoring/removing of glutamate receptors at spine heads, and may control the efficacy of existing synapses.

Introduction

Little progress in the understanding of the cellular mechanisms underlying dendritic spine plasticity has been made since spines were first described over a century ago. Using high resolution imaging, it is now possible to study the factors that regulate spine formation, and to examine the functional relevance of the heterogeneity of spine morphologies in living neurons. The results of these recent studies will be reviewed here. In combination with fluorescent tagging of molecules, these high resolution, sensitive imaging methods will allow the sequencing of the molecular events that lead to modifications of spine morphology and function.

Section snippets

Spine synapses are excitatory and changeable

The first indication that dendritic spines are the locus of excitatory synaptic connections came from electron microscopic observations by Gray [1], who proposed that synapses consisting of a presynaptic bouton in contact with a dendritic spine would have an excitatory effect. This proposal received experimental support through the study of four different hippocampal pathways, all of which had been demonstrated to have an excitatory effect on pyramidal or dentate granule cells. When subjected

Spines display unique Ca2+ dynamics

Over the past decade it has become apparent that the dendritic spine is a unique Ca2+ compartment; the increase of intracellular Ca2+ concentration ([Ca2+]i) following synaptic stimulation can be restricted to individual spines [6radical dot7radical dot8radical dot]. The elevation of [Ca2+]i in an individual spine can result from influx via voltage-gated Ca2+ channels, as is the case with back-propagating action potentials, or via activation of synaptic glutamate channels of the NMDA type [9], or through release from Ca2+

Changes in spine morphology vary greatly in speed

Although spines show a remarkable persistence over time, young spines may change both extensively and quickly. Such alterations may vary from small ruffle-like changes of the surface membrane on a scale of seconds [13] to large rearrangements of the entire spine and, indeed, the emergence of entirely new spines or total removal of existing spines [14], [15], [16], [17], [18]. Both the formation and the removal of spines may occur at rates varying between tens of minutes and a few hours [19radical dot[20]]

Spines have a large repertoire of changes

During normal development and under conditions of synaptic plasticity, alterations of spine form and size range from molecular adjustments to large-scale changes such as removal or generation of entire new spines. Most of the shape changes are probably driven by polymerisation of actin filaments. Intense glutamate activation causes a fast and dramatic loss of dendritic spines, paralleled by a loss of filamentous actin [28]. Volatile anaesthetics in clinical doses block spine membrane changes as

Physiological spine changes

A number of studies indicate that physiological processes may be directly linked to spine changes. Reduction of synaptic input by the removal of whiskers in young rats has been shown to cause a large compensatory increase in the number and size of spines on pyramidal cells of the ipsilateral barrel field [15]. Hibernating squirrels have shorter dendrites and fewer spines in the middle of hibernation compared to during their active periods and the changes return to normal within 2 hr after

Experimental spine changes seen in acute slices

Little is known of the factors which preserve spines. Both deafferentation and tetrodotoxin-inactivation of Purkinje cells cause an increase in the number of spines on proximal dendrites [21]. In hippocampal slice cultures, spontaneous miniature synaptic potentials mediated by AMPA receptors maintain dendritic spines [43radical dotradical dot]. In contrast, delivery of brain-derived neurotrophic factor (BDNF) to cortical pyramidal cells causes sprouting of their basal dendrites but a reduction of spine number,

Conclusions

Although rapid progress has been made during the past year in the characterisation of dendritic spine motility, many questions remain unanswered. The functional relevance of spine motility and shape is not clear. Only recently have we begun to appreciate that observations of spine motility made in vitro are reproduced in vivo [50radical dotradical dot]. Finally, the rules governing the formation of spines and their transition from one shape to another are still not known. On the bright side, it is expected that the

Acknowledgements

We would like to thank Dr E Korkotian for the use of the unpublished figure of a labeled dendrite.

References and recommended reading

Papers of particular interest, published within the annual period of review,have been highlighted as:

  • radical dot of special interest

  • radical dotradical dot of outstanding interest

References (50)

  • P Andersen et al.

    Location and identification of excitatory synapses on hippocampal pyramidal cells

    Exp Brain Res

    (1966)
  • LE Westrum et al.

    An electron microscopic study of the stratum radiatum of the rat hippocampus (regio superior, CA1) with particular emphasis on synaptology

    J Comp Neurol

    (1962)
  • KM Harris et al.

    Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function

    Annu Rev Neurosci

    (1994)
  • SR Ramon y Cajal

    Estructura del asta del Ammon

    Anal Soc esp Hist Nat Madr

    (1893)
  • R Yuste et al.

    Mechanisms of calcium influx into hippocampal spines: heterogeneity among spines, coincidence detection by NMDA receptors, and optical quantal analysis

    J Neurosci

    (1999)
  • Y Kovalchuk et al.

    NMDA receptor mediated subthreshold Ca2+ signals in spines of hippocampal neurons

    J Neurosci

    (2000)
  • M Segal

    Imaging of calcium variations in dendritic spines of cultured hippocampal neurons

    J Physiol

    (1995)
  • E Korkotian et al.

    Fast confocal imaging of calcium released from stores in dendritic spines

    Eur J Neurosci

    (1998)
  • N Volfovsky et al.

    Geometry of dendritic spines affects calcium dynamics in hippocampal neurons: theory and experiments

    J Neurophysiol

    (1999)
  • A Majewska et al.

    Mechanisms of calcium decay kinetics in hippocampal spines: role of spine calcium pumps and calcium diffusion through the spine neck in biochemical compartmentalization

    J Neurosci

    (2000)
  • AM Vees et al.

    Increased number and size of dendritic spines in ipsilateral barrel field cortex following unilateral whisker trimming in postnatal rat

    J Comp Neurol

    (1998)
  • J Bock et al.

    Differential emotional experience leads to pruning of dendritic spines in the forebrain of domestic chicks

    Neural Plast

    (1998)
  • J Bock et al.

    Blockade of N-methyl-d-aspartate receptor activation suppresses learning-induced synaptic elimination

    Proc Natl Acad Sci USA

    (1999)
  • HW Horch et al.

    Destabilization of cortical dendrites and spines by BDNF

    Neuron

    (1999)
  • A Dunaevsky et al.

    Developmental regulation of spine motility in the mammalian central nervous system

    Proc Natl Acad Sci USA

    (1999)
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