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Neural Plasticity 2016Structural plasticity of excitatory synapses is a vital component of neuronal development, synaptic plasticity, and behaviour. Abnormal development or regulation of... (Review)
Review
Structural plasticity of excitatory synapses is a vital component of neuronal development, synaptic plasticity, and behaviour. Abnormal development or regulation of excitatory synapses has also been strongly implicated in many neurodevelopmental, psychiatric, and neurodegenerative disorders. In the mammalian forebrain, the majority of excitatory synapses are located on dendritic spines, specialized dendritic protrusions that are enriched in actin. Research over recent years has begun to unravel the complexities involved in the regulation of dendritic spine structure. The small GTPase family of proteins have emerged as key regulators of structural plasticity, linking extracellular signals with the modulation of dendritic spines, which potentially underlies their ability to influence cognition. Here we review a number of studies that examine how small GTPases are activated and regulated in neurons and furthermore how they can impact actin dynamics, and thus dendritic spine morphology. Elucidating this signalling process is critical for furthering our understanding of the basic mechanisms by which information is encoded in neural circuits but may also provide insight into novel targets for the development of effective therapies to treat cognitive dysfunction seen in a range of neurological disorders.
Topics: Animals; Brain; Dendritic Spines; Humans; Microfilament Proteins; Monomeric GTP-Binding Proteins; Neuronal Plasticity; Neurons; Signal Transduction
PubMed: 26989514
DOI: 10.1155/2016/3025948 -
The Neuroscientist : a Review Journal... Dec 2010Dendritic spines are small actin-rich protrusions that form the postsynaptic part of most excitatory synapses. They play critical roles in synaptic function and exhibit... (Review)
Review
Dendritic spines are small actin-rich protrusions that form the postsynaptic part of most excitatory synapses. They play critical roles in synaptic function and exhibit a striking degree of structural plasticity, which is closely linked to changes in strength of synaptic connections. Here the authors summarize recent work that has revealed an important relationship between the microtubule and actin cytoskeleton in controlling spine morphology and plasticity. Dynamic microtubules and the proteins that specifically associate with the growing microtubule plus-ends recently emerged as temporal and spatial regulators of actin organization, which controls dynamic changes in structure and function of dendritic spines.
Topics: Actin Cytoskeleton; Amino Acid Sequence; Animals; Dendritic Spines; Humans; Microtubules; Molecular Sequence Data; Nerve Tissue Proteins; Neuronal Plasticity
PubMed: 21239729
DOI: 10.1177/1073858410386357 -
Neuron May 2005Dendritic spines are tiny protrusions on dendritic shafts where most excitatory synapses are located. Recent advances in imaging technologies have given us great insight... (Review)
Review
Dendritic spines are tiny protrusions on dendritic shafts where most excitatory synapses are located. Recent advances in imaging technologies have given us great insight into the function of spines as biochemical compartments. Here we review recent evidence suggesting that the geometry of dendritic spines controls postsynaptic calcium signaling and is bidirectionally regulated during synaptic plasticity.
Topics: Animals; Calcium; Dendritic Spines; Models, Neurological; Neuronal Plasticity; Receptors, Glutamate; Signal Transduction
PubMed: 15944122
DOI: 10.1016/j.neuron.2005.05.006 -
Current Opinion in Neurobiology Jun 2012The specialized morphology of dendritic spines creates an isolated compartment that allows for localized biochemical signaling. Recent studies have revealed complexity... (Review)
Review
The specialized morphology of dendritic spines creates an isolated compartment that allows for localized biochemical signaling. Recent studies have revealed complexity in the function of the spine head as a signaling domain and indicate that (1) the spine is functionally subdivided into multiple independent microdomains and (2) not all biochemical signals are equally compartmentalized within the spine. Here we review these findings as well as the developments in fluorescence microscopy that are making possible direct monitoring of signaling within spines and, in the future, within sub-spine microdomains.
Topics: Animals; Dendritic Spines; Membrane Microdomains; Models, Biological; Signal Transduction; Synapses
PubMed: 22459689
DOI: 10.1016/j.conb.2012.03.003 -
The Neuroscientist : a Review Journal... Apr 2010The spine apparatus (SA) is an essential component of mature dendritic spines of cortical and hippocampal neurons, yet its functions are still enigmatic. Synaptopodin... (Review)
Review
The spine apparatus (SA) is an essential component of mature dendritic spines of cortical and hippocampal neurons, yet its functions are still enigmatic. Synaptopodin (SP), an actin-binding protein, colocalizes with the SA. Hippocampal neurons in SP-knockout mice lack SA, and they express lower LTP. SP probably plays a role in synaptic plasticity, but only recently it is being linked mechanistically to synaptic functions. These authors and others have studied endogenous and transfected SP in dendritic spines of cultured hippocampal neurons. They found that spines containing SP generate twice as large responses to flash photolysis of caged glutamate than SP-negative ones. An N-methyl-d-aspartate receptor-mediated chemical LTP caused accumulation of GFP-GluR1 in spine heads of control but not of shRNA transfected, SP-deficient neurons. SP is linked to calcium stores, because their pharmacological blockade eliminated SP-related enhancement of glutamate responses. Furthermore, release of calcium from stores produces an SP-dependent delivery of GluR1 into spines. Thus, SP plays a crucial role in the calcium store-associated ability of neurons to undergo long-term plasticity.
Topics: Animals; Calcium; Dendritic Spines; Hippocampus; Humans; Mice; Microfilament Proteins; Neuronal Plasticity
PubMed: 20400711
DOI: 10.1177/1073858409355829 -
Molecular and Cellular Neurosciences Oct 2017Dendritic spines are small actin-rich protrusions from neuronal dendrites that form the postsynaptic part of most excitatory synapses. Changes in the number or strength... (Review)
Review
Dendritic spines are small actin-rich protrusions from neuronal dendrites that form the postsynaptic part of most excitatory synapses. Changes in the number or strength of synapses are physiological mechanisms behind learning. The growth and maturation of dendritic spines and the activity-induced changes to their morphology are all based on changes to the actin cytoskeleton. In this review, we will discuss the regulation of the actin cytoskeleton in dendritic spine formation and maturation, as well as in synaptic strengthening. Concerning spine formation, we will focus on spine initiation, which has received less attention in the literature. We will also examine the recently revealed regulation of the actin cytoskeleton through post-translational modifications of actin monomers, in addition to the conventional regulation of actin via actin-binding proteins.
Topics: Actin Cytoskeleton; Actins; Animals; Dendritic Spines; Humans; Microfilament Proteins; Neuronal Plasticity; Synapses
PubMed: 28479292
DOI: 10.1016/j.mcn.2017.05.002 -
Biomolecules Aug 2023Dendritic spines are actin-rich protrusions that receive a signal from the axon at the synapse. Remodeling of cytoskeletal actin is tightly connected to dendritic spine...
Dendritic spines are actin-rich protrusions that receive a signal from the axon at the synapse. Remodeling of cytoskeletal actin is tightly connected to dendritic spine morphology-mediated synaptic plasticity of the neuron. Remodeling of cytoskeletal actin is required for the formation, development, maturation, and reorganization of dendritic spines. Actin filaments are highly dynamic structures with slow-growing/pointed and fast-growing/barbed ends. Very few studies have been conducted on the role of pointed-end binding proteins in the regulation of dendritic spine morphology. In this study, we evaluated the role played by tropomodulin 2 (Tmod2)-a brain-specific isoform, on the dendritic spine re-organization. Tmod2 regulates actin nucleation and polymerization by binding to the pointed end via actin and tropomyosin (Tpm) binding sites. We studied the effects of Tmod2 overexpression in primary hippocampal neurons on spine morphology using confocal microscopy and image analysis. Tmod2 overexpression decreased the spine number and increased spine length. Destroying Tpm-binding ability increased the number of shaft synapses and thin spine motility. Eliminating the actin-binding abilities of Tmod2 increased the number of mushroom spines. Tpm-mediated pointed-end binding decreased F-actin depolymerization, which may positively affect spine stabilization; the nucleation ability of Tmod2 appeared to increase shaft synapses.
Topics: Actins; Dendritic Spines; Tropomodulin; Actin Cytoskeleton; Cytoskeleton
PubMed: 37627302
DOI: 10.3390/biom13081237 -
Current Opinion in Neurobiology Aug 2016Synapses are the basic unit of neuronal communication and their disruption is associated with many neurological disorders. Significant progress has been made towards... (Review)
Review
Synapses are the basic unit of neuronal communication and their disruption is associated with many neurological disorders. Significant progress has been made towards understanding the molecular and genetic regulation of synapse formation, modulation, and dysfunction, but the underlying cellular mechanisms remain incomplete. The actin cytoskeleton not only provides the structural foundation for synapses, but also regulates a diverse array of cellular activities underlying synaptic function. Here we will discuss the regulation of the actin cytoskeleton in dendritic spines, the postsynaptic compartment of excitatory synapses. We will focus on a select number of actin regulatory processes, highlighting recent advances, the complexity of crosstalk between different pathways, and the challenges of understanding their precise impact on the structure and function of synapses.
Topics: Actin Cytoskeleton; Dendritic Spines; Humans; Neurogenesis; Neuronal Plasticity; Synapses
PubMed: 27138585
DOI: 10.1016/j.conb.2016.04.010 -
ACS Chemical Neuroscience May 2023Quantitative methods for assessing neural anatomy have rapidly evolved in neuroscience and provide important insights into brain health and function. However, as new... (Review)
Review
Quantitative methods for assessing neural anatomy have rapidly evolved in neuroscience and provide important insights into brain health and function. However, as new techniques develop, it is not always clear when and how each may be used to answer specific scientific questions posed. Dendritic spines, which are often indicative of synapse formation and neural plasticity, have been implicated across many brain regions in neurodevelopmental disorders as a marker for neural changes reflecting neural dysfunction or alterations. In this Perspective we highlight several techniques for staining, imaging, and quantifying dendritic spines as well as provide a framework for avoiding potential issues related to pseudoreplication. This framework illustrates how others may apply the most rigorous approaches. We consider the cost-benefit analysis of the varied techniques, recognizing that the most sophisticated equipment may not always be necessary for answering some research questions. Together, we hope this piece will help researchers determine the best strategy toward using the ever-growing number of techniques available to determine neural changes underlying dendritic spine morphology in health and neurodevelopmental disorders.
Topics: Humans; Dendritic Spines; Neurodevelopmental Disorders; Neuronal Plasticity; Brain
PubMed: 37070364
DOI: 10.1021/acschemneuro.3c00062 -
The Journal of Physiology Jan 2010In the central nervous system, most excitatory synapses occur on dendritic spines, which are small protrusions from the dendritic tree. In the mature cortex and... (Review)
Review
In the central nervous system, most excitatory synapses occur on dendritic spines, which are small protrusions from the dendritic tree. In the mature cortex and hippocampus, dendritic spines are heterogeneous in shape. It has been shown that the shapes of the spine can affect synapse stability and synaptic function. Dendritic spines are highly motile structures that can undergo actin-dependent shape changes, which occur over a time scale ranging from seconds to tens of minutes or even days. The formation, remodelling and elimination of excitatory synapses on dendritic spines represent ways of refining the microcircuitry in the brain. Here I review the current knowledge on the effects of modulation of AMPA and NMDA ionotropic glutamate receptors on dendritic spine formation, motility and remodelling.
Topics: Animals; Brain; Dendritic Spines; Excitatory Amino Acids; Excitatory Postsynaptic Potentials; Humans; Neuronal Plasticity; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate
PubMed: 19933758
DOI: 10.1113/jphysiol.2009.178905