Morphological Changes in Dendritic Spines Associated with Long-Term Synaptic Plasticity

Abstract

Dendritic spines are morphological specializations that receive synaptic inputs and compartmentalize calcium. In spite of a long history of research, the specific function of spines is still not well understood. Here we review the current status of the relation between morphological changes in spines and synaptic plasticity. Since Cajal and Tanzi proposed that changes in the structure of the brain might occur as a consequence of experience, the search for the morphological correlates of learning has constituted one of the central questions in neuroscience. Although there are scores of studies that encompass this wide field in many species, in this review we focus on experimental work that has analyzed the morphological consequences of hippocampal long-term potentiation (LTP) in rodents. Over the past two decades many studies have demonstrated changes in the morphology of spines after LTP, such as enlargements of the spine head and shortenings of the spine neck. Biophysically, these changes translate into an increase in the synaptic current injected at the spine, as well as shortening of the time constant for calcium compartmentalization. In addition, recent online studies using time-lapse imaging have reported increased spinogenesis. The currently available data show a strong correlation between synaptic plasticity and morphological changes in spines, although at the same time, there is no evidence that these morphological changes are necessary or sufficient for the induction or maintenance of LTP. Still, they highlight once more how form and function go hand in hand in the central nervous system.

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

“…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).…”

“…Considering that long and thin spines may isolate synaptically initiated spine Ca 2+ transients from the parent dendrite and neighboring spines , and that synchronously coordinated dendritic and spine Ca 2+ transients are critical for synaptic plasticity (Yuste and Bonhoeffer, 2001;Sabatini et al, 2001), BDNF may enhance synaptic plasticity not only by increasing spine density, but also the proportion of Type-I stubby spines. These larger spines with wider necks are thought to represent spines that acquired AMPA receptors immediately after the induction of long-term potentiation (Matsuzaki et al, 2001;Kasai et al, 2003), and thus enhance spine-dendrite coupling leading to widespread dendritic Ca 2+ signaling during excitatory synaptic transmission (Noguchi et al, 2005).…”

Rho-linked genes and neurological disorders

“…Significantly, recent studies by Govek et al showed that knock-down of OPHN1 expression in CA1 pyramidal neurons in hippocampal slices results in a significant decrease in dendritic spine length [30]. As spine morphology is ultimately linked to synaptic function [89], such spine morphological changes are likely to compromise synaptic plasticity, and potentially lead to learning and memory deficits. The above spine length phenotype was mimicked using a constitutive active RhoA (CA-RhoA) mutant and could be largely rescued by inhibiting the RhoA effector, Rho-kinase (Govek et al 2004).…”

“…These dynamic changes are determined by the architecture of its actin cytoskeleton [94]. Significantly, increasing evidence indicates that proper regulation of spine shape and size is crucial for processing of information [13,44,52,55,89]. For instance, spine morphology and/or dynamics have been associated with long-term potentiation (LTP) and long term-depression (LTD), which are two well studied forms of learning and memory [55].…”

Synaptic plasticity in early aging

“…We prefer the original Lynch and Baudry proposal that changes in receptor number are secondary to changes in the size of the synaptic zone (the post synaptic density, psd), which themselves are secondary to alterations in spine morphology. The original impetus for this idea came from ultrastructural studies showing that shifts in spine and psd morphology accompany LTP (Lee et al, 1980), an observation subsequently greatly expanded by analyses with electron microscopic (Yuste and Bonhoeffer, 2001 for review) and newly developed light microscopic Lin et al, 2005) methods.…”