Biology Reference
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inhibitory synapses are made onto spines. A spine with an inhibitory synapse always carries
an excitatory synapse as well (Beaulieu and Colonnier, 1989). Given the dominance of
excitatory synapses, about 15% of all dendritic spines carry both excitatory and inhibitory
synaptic profiles, as in the case of the striatum, structure that is the main target of this chapter.
One possible function of dendritic spines is the increase of the surface area of dendrites
and thus the number of possible synapses per dendritic length. Furthermore, spines allow
dendrites to reach multiple axons, minimizing the distances from one synapse to the next. In
addition, the narrow spine neck restricts the diffusion of molecules into and out of the spine
(Nimchimsky et al., 2002). This diffusional biochemical compartmentalization may help to
retain molecules at the synapse, i.e. Ca
2+
influx upon synaptic stimulation is limited to the
stimulated spine and does not affect synapses on neighboring spines (Sabatini et al., 2001;
Nimchimsky et al., 2002).
Spines may be isolated functional entities at times; calcium influx from NMDA receptors
or calcium channels activated by weak synaptic inputs may cause an increase in calcium
concentration within the spine (Yuste et al., 2000). This may lead to the activation of
signaling cascades other than membrane potential changes. For instance, the length and shape
of the spine neck, which determines how well the synaptic potentials that are generated within
a spine will spread to the dendritic shaft, could conceivably vary with cytoskeletal
rearrangements that are dependent on this calcium influx (Matus, 2000). It has been proposed
that a moderate increase of cytoplasmic calcium concentration causes elongation of spines,
whereas a very large increase of calcium concentration causes shrinkage and collapse of
spines (Segal et al., 2005). The possible deleterious effects of high concentrations of Ca
2+
produced by excitatory synaptic activity have suggested the hypothesis that “a major role of
spines is to protect the parent dendrite from a rise of Ca
2+
to levels that can be toxic to the
cell” (Shepherd, 1996).
Although recent imaging studies have focused on spine formation and pruning, or on
spine expansion and shrinkage, electron microscopy reconstruction studies have led to
discoveries of other types of change in spines. These include changes in the length of the
postsynaptic density at the spine head (Desmond and Levy, 1986), spine splitting (Edwards,
1995), the formation of perforated spines (Geinisman et al., 1987, 1988; 2001; Geinisman,
2000, and others) changes in spine curvature and the formation of multiple spine synapses
(Toni et al., 1999). Some authors have attempted to provide a unified view that considers the
different spine changes as subclasses of postsynaptic density enlargement (Harris et al.,
2003).
Pathological changes in spines can be classified into two general categories, pathologies
of distribution and pathologies of structure. Pathologies of distribution include dramatic
increases and decreases in spine density, and widespread changes in morphology. Commonly
observed morphological changes include an overall reduction in spine size or alteration in
spine shape, dendritic beading with concomitant loss of spines, and sprouting of spines in
abnormal locations. Pathologies of structure include all those changes observable in single
spines, such as densification of the cytoplasm, hypertrophy of organelles or spine volume, and
formation of aberrant synapse-like connections (Fiala et al., 2002).
The loss of spines upon deafferentation suggests that they are somehow maintained by
their afferent input. Because spines bear glutamatergic synapses, one may reason that some
aspect of glutamatergic neurotransmission acts as a signal to maintain the spine and that
interference with normal synaptic activity may therefore affect spine shape or density
