ReviewDendritic spines shaped by synaptic activity
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 [678]. 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 [19[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 [43]. 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 [50]. 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:
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