The majority of the postsynaptic terminals of excitatory synapses in the central nervous system exist on small bulbous structures on dendrites known as dendritic spines. The actin cytoskeleton is a structural element underlying the proper development and morphology of dendritic spines. Synaptic activity patterns rapidly change actin dynamics, leading to morphological changes in dendritic spines. In this mini-review, we will discuss recent findings on neuronal maturation and synaptic plasticityinduced changes in the dendritic spine actin cytoskeleton. We propose that actin dynamics in dendritic spines decrease through actin filament crosslinking during neuronal maturation. In long-term potentiation, we evaluate the model of fast breakdown of actin filaments through severing and rebuilding through polymerization and later stabilization through crosslinking. We will discuss the role of Ca 21 in long-term depression, and suggest that actin filaments are dissolved through actin filament severing. V C 2016 Wiley Periodicals, Inc.Key Words: dendritic spines; actin cytoskeleton; neuronal maturation; synaptic plasticity Introduction T he majority of postsynaptic terminals of excitatory synapses in the central nervous system exist on small bulbous structures on neuronal dendrites known as dendritic spines. Dendritic spines can be divided into three morphological categories: thin, consisting of a long thin neck and a small round head; stubby, with a large bulbous head and a short wide neck; and mushroom, characterized by a large bulbous head and a short narrow neck [Bourne and Harris, 2008]. Dendritic spine maturation is a process where the postsynaptic machinery is recruited to the newly formed spine and the spine acquires a more stable, usually mushroom-shaped morphology [Dailey and Smith, 1996;Dunaevsky et al., 1999]. The shape and size of the spine head and neck have been shown to influence the electrical properties and compartmentalization of the spine [Noguchi et al., 2005] and morphological changes were shown to account for changes in synaptic function [Yuste and Bonhoeffer, 2001]. Accordingly, synaptic activity is translated into structural changes in dendritic spines and functional changes in synaptic efficacy.The actin cytoskeleton is a structural element underlying the proper development and morphology of dendritic spines, where it controls the morphological and structural changes induced by synapse activation. Actin filaments are polar structures with one end growing more rapidly (the plus or "barbed" end) than the other (the minus or "pointed" end). The constant removal of actin subunits from the pointed ends and addition at the barbed ends is known as actin treadmilling. Filamentous (F-) actin structures range from a branched filament network to thick bundles of several crosslinked filaments [Blanchoin et al., 2014]. These structures have highly variable lifetimes. Filaments forming the actin mesh can change very rapidly whereas thick actin bundles can remain stable for a long time. Based on the turnover rate...

In this study, we performed a comprehensive behavioral and anatomical analysis of the Missing in Metastasis (Mtss1/MIM) knockout (KO) mouse brain. We also analyzed the expression of MIM in different brain regions at different ages. MIM is an I-BAR containing membrane curving protein, shown to be involved in dendritic spine initiation and dendritic branching in Purkinje cells in the cerebellum. Behavioral analysis of MIM KO mice revealed defects in both learning and reverse-learning, alterations in anxiety levels and reduced dominant behavior, and confirmed the previously described deficiency in motor coordination and pre-pulse inhibition. Anatomically, we observed enlarged brain ventricles and decreased cortical volume. Although MIM expression was relatively low in hippocampus after early development, hippocampal pyramidal neurons exhibited reduced density of thin and stubby dendritic spines. Learning deficiencies can be connected to all detected anatomical changes. Both behavioral and anatomical findings are typical for schizophrenia mouse models.

Many actin cytoskeleton-regulating proteins control dendritic spine morphology and density, which are cellular features often altered in autism spectrum disorder (ASD). Recent studies using animal models show that autism-related behavior can be rescued by either manipulating actin regulators or by reversing dendritic spine density or morphology. Based on these studies, the actin cytoskeleton is a potential target pathway for developing new ASD treatments. Thus, it is important to understand how different ASD-associated actin regulators contribute to the regulation of dendritic spines and how ASD-associated mutations modulate this regulation. For this study, we selected five genes encoding different actin-regulating proteins and induced ASD-associated de novo missense mutations in these proteins. We assessed the functionality of the wild-type and mutated proteins by analyzing their subcellular localization, and by analyzing the dendritic spine phenotypes induced by the expression of these proteins. As the imbalance between excitation and inhibition has been suggested to have a central role in ASD, we additionally evaluated the density, size and subcellular localization of inhibitory synapses. Common for all the proteins studied was the enrichment in dendritic spines. ASD-associated mutations induced changes in the localization of α-actinin-4, which localized less to dendritic spines, and for SWAP-70 and SrGAP3, which localized more to dendritic spines. Among the wild-type proteins studied, only α-actinin-4 expression caused a significant change in dendritic spine morphology by increasing the mushroom spine density and decreasing thin spine density. We hypothesized that mutations associated with ASD shift dendritic spine morphology from mushroom to thin spines. An M554V mutation in α-actinin-4 (ACTN4) resulted in the expected shift in dendritic spine morphology by increasing the density of thin spines. In addition, we observed a trend toward higher thin spine density with mutations in myosin IXb and SWAP-70. Myosin IIb and myosin IXb expression increased the proportion of inhibitory synapses in spines. The expression of mutated myosin IIb (Y265C), SrGAP3 (E469K), and SWAP-70 (L544F) induced variable changes in inhibitory synapses.

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