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Developmental Biology Aug 2022The morphogenesis and plasticity of dendritic spines are associated with synaptic strength, learning, and memory. Dendritic spines are highly compartmentalized... (Review)
Review
The morphogenesis and plasticity of dendritic spines are associated with synaptic strength, learning, and memory. Dendritic spines are highly compartmentalized structures, which makes proteins involved in cellular polarization and membrane compartmentalization likely candidates regulating their formation and maintenance. Indeed, recent studies suggest polarity proteins help form and maintain dendritic spines by compartmentalizing the spine neck and head. Here, we review emerging evidence that polarity proteins regulate dendritic spine plasticity and stability through the cytoskeleton, scaffolding molecules, and signaling molecules. We specifically analyze various polarity complexes known to contribute to different forms of cell polarization processes and examine the essential conceptual context linking these groups of polarity proteins to dendritic spine morphogenesis, plasticity, and cognitive functions.
Topics: Cytoskeleton; Dendritic Spines; Morphogenesis; Neuronal Plasticity; Signal Transduction; Synapses
PubMed: 35580729
DOI: 10.1016/j.ydbio.2022.05.007 -
Cerebellum (London, England) 2005Shapes of dendritic spines are changed by various physiological or pathological states. The high degree of spine shape heterogeneity suggests that they would be the... (Review)
Review
Shapes of dendritic spines are changed by various physiological or pathological states. The high degree of spine shape heterogeneity suggests that they would be the morphological basis for synaptic plasticity. An increasing number of proteins and signal transduction pathways have recently been shown to be associated with structural modifications of spines. Here, we review the possible functional roles of spine shapes in cerebellar Purkinje neurons. Several studies have suggested that spine shapes in Purkinje cells are regulated by both intrinsic and environmental factors, and different spine shapes could have significantly different consequences for brain function. Clearly constricted necks observed in thin, mushroom-shaped, and branched spines serve for compartmentalization of calcium and other second messenger molecules, influencing different signaling mechanisms and synaptic plasticity. Mushroom-shaped spines frequently have perforated postsynaptic density and the area of the spine head is much larger than simple spines, implying that membrane dynamics and receptor turnover are occurring. Branched spines might form additional synapses with afferent inputs resulting in the modification of neuronal circuits. Taken together, all these studies suggest that each spine shape is likely to have a distinct role in Purkinje cell function.
Topics: Animals; Cerebellum; Dendritic Spines; Humans; Neuronal Plasticity; Purkinje Cells
PubMed: 16035191
DOI: 10.1080/14734220510007842 -
Journal of Neurophysiology Mar 2015Hyperreflexia and spasticity are chronic complications in spinal cord injury (SCI), with limited options for safe and effective treatment. A central mechanism in...
Hyperreflexia and spasticity are chronic complications in spinal cord injury (SCI), with limited options for safe and effective treatment. A central mechanism in spasticity is hyperexcitability of the spinal stretch reflex, which presents symptomatically as a velocity-dependent increase in tonic stretch reflexes and exaggerated tendon jerks. In this study we tested the hypothesis that dendritic spine remodeling within motor reflex pathways in the spinal cord contributes to H-reflex dysfunction indicative of spasticity after contusion SCI. Six weeks after SCI in adult Sprague-Dawley rats, we observed changes in dendritic spine morphology on α-motor neurons below the level of injury, including increased density, altered spine shape, and redistribution along dendritic branches. These abnormal spine morphologies accompanied the loss of H-reflex rate-dependent depression (RDD) and increased ratio of H-reflex to M-wave responses (H/M ratio). Above the level of injury, spine density decreased compared with below-injury spine profiles and spine distributions were similar to those for uninjured controls. As expected, there was no H-reflex hyperexcitability above the level of injury in forelimb H-reflex testing. Treatment with NSC23766, a Rac1-specific inhibitor, decreased the presence of abnormal dendritic spine profiles below the level of injury, restored RDD of the H-reflex, and decreased H/M ratios in SCI animals. These findings provide evidence for a novel mechanistic relationship between abnormal dendritic spine remodeling in the spinal cord motor system and reflex dysfunction in SCI.
Topics: Aminoquinolines; Animals; Dendritic Spines; H-Reflex; Male; Motor Neurons; Pyrimidines; Rats; Rats, Sprague-Dawley; Reflex, Abnormal; Spinal Cord Injuries
PubMed: 25505110
DOI: 10.1152/jn.00566.2014 -
Organization and dynamics of the actin cytoskeleton during dendritic spine morphological remodeling.Cellular and Molecular Life Sciences :... Aug 2016In the central nervous system, most excitatory post-synapses are small subcellular structures called dendritic spines. Their structure and morphological remodeling are... (Review)
Review
In the central nervous system, most excitatory post-synapses are small subcellular structures called dendritic spines. Their structure and morphological remodeling are tightly coupled to changes in synaptic transmission. The F-actin cytoskeleton is the main driving force of dendritic spine remodeling and sustains synaptic plasticity. It is therefore essential to understand how changes in synaptic transmission can regulate the organization and dynamics of actin binding proteins (ABPs). In this review, we will provide a detailed description of the organization and dynamics of F-actin and ABPs in dendritic spines and will discuss the current models explaining how the actin cytoskeleton sustains both structural and functional synaptic plasticity.
Topics: Actin Cytoskeleton; Actins; Animals; Dendritic Spines; Humans; Microfilament Proteins; Neuronal Plasticity; Signal Transduction; Synapses
PubMed: 27105623
DOI: 10.1007/s00018-016-2214-1 -
Current Protocols May 2023In recent decades, mounting evidence has shown that microglia play a vital role in maintaining synapses throughout life. This maintenance is done via numerous microglial...
In recent decades, mounting evidence has shown that microglia play a vital role in maintaining synapses throughout life. This maintenance is done via numerous microglial processes, which are long, thin, and highly motile protrusions from the cell body that monitor their environment. However, due to the brevity of the contacts and the potentially transient nature of synaptic structures, establishing the underlying dynamics of this relationship has proven difficult. This article describes a method of using rapidly acquired multiphoton microscopy images to track microglial dynamics and microglia:synapse interactions and the fate of the synaptic structures following those interactions. First, we detail a method for capturing multiphoton images at 1-min intervals for approximately 1 hr and how that process can be done at multiple time points. We then discuss how best to prevent and account for any drifting of the region of interest that can occur during the imaging session and how to remove excessive background noise from those images. Finally, we detail the annotation process for dendritic spines and microglial processes using plugins in MATLAB and Fiji, respectively. These semi-automated plugins allow tracking of individual cell structures, even if both microglia and neurons are imaged in the same fluorescent channel. This protocol presents a method of tracking both microglial dynamics and synaptic structures, in the same animal, at multiple time points, giving the user information on process speed, branching, tip size, location, and dwell time, as well as any dendritic spine gains, losses, and size changes. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Rapid multiphoton image capture Basic Protocol 2: Image preparation using MATLAB and Fiji Basic Protocol 3: Dendritic spine and microglial processes annotation using ScanImage and TrackMate.
Topics: Animals; Dendritic Spines; Microglia; Microscopy; Cell Body; Coloring Agents
PubMed: 37222240
DOI: 10.1002/cpz1.791 -
Neural Plasticity 2016The asymmetric distribution of various proteins and RNAs is essential for all stages of animal development, and establishment and maintenance of this cellular polarity... (Review)
Review
The asymmetric distribution of various proteins and RNAs is essential for all stages of animal development, and establishment and maintenance of this cellular polarity are regulated by a group of conserved polarity determinants. Studies over the last 10 years highlight important functions for polarity proteins, including apical-basal polarity and planar cell polarity regulators, in dendritic spine development and plasticity. Remarkably, many of the conserved polarity machineries function in similar manners in the context of spine development as they do in epithelial morphogenesis. Interestingly, some polarity proteins also utilize neuronal-specific mechanisms. Although many questions remain unanswered in our understanding of how polarity proteins regulate spine development and plasticity, current and future research will undoubtedly shed more light on how this conserved group of proteins orchestrates different pathways to shape the neuronal circuitry.
Topics: Animals; Cell Polarity; Dendritic Spines; Humans; Neurogenesis; Neuronal Plasticity; Neurons
PubMed: 26839714
DOI: 10.1155/2016/3145019 -
The Journal of General Physiology Aug 2019Dendritic spines are small subcompartments that protrude from the dendrites of neurons and are important for signaling activity and synaptic communication. These...
Dendritic spines are small subcompartments that protrude from the dendrites of neurons and are important for signaling activity and synaptic communication. These subcompartments have been characterized to have different shapes. While it is known that these shapes are associated with spine function, the specific nature of these shape-function relationships is not well understood. In this work, we systematically investigated the relationship between the shape and size of both the spine head and spine apparatus, a specialized endoplasmic reticulum compartment within the spine head, in modulating rapid calcium dynamics using mathematical modeling. We developed a spatial multicompartment reaction-diffusion model of calcium dynamics in three dimensions with various flux sources, including N-methyl-D-aspartate receptors (NMDARs), voltage-sensitive calcium channels (VSCCs), and different ion pumps on the plasma membrane. Using this model, we make several important predictions. First, the volume to surface area ratio of the spine regulates calcium dynamics. Second, membrane fluxes impact calcium dynamics temporally and spatially in a nonlinear fashion. Finally, the spine apparatus can act as a physical buffer for calcium by acting as a sink and rescaling the calcium concentration. These predictions set the stage for future experimental investigations of calcium dynamics in dendritic spines.
Topics: Animals; Calcium; Calcium Channels; Calcium Signaling; Dendritic Spines; Models, Theoretical; Rats; Receptors, N-Methyl-D-Aspartate
PubMed: 31324651
DOI: 10.1085/jgp.201812261 -
Molecular Pain Jan 2017Neuropathic pain is a major complication of spinal cord injury, and despite aggressive efforts, this type of pain is refractory to available clinical treatment. Our...
Neuropathic pain is a major complication of spinal cord injury, and despite aggressive efforts, this type of pain is refractory to available clinical treatment. Our previous work has demonstrated a structure-function link between dendritic spine dysgenesis on nociceptive sensory neurons in the intermediate zone, laminae IV/V, and chronic pain in central nervous system and peripheral nervous system injury models of neuropathic pain. To extend these findings, we performed a follow-up structural analysis to assess whether dendritic spine remodeling occurs on superficial dorsal horn neurons located in lamina II after spinal cord injury. Lamina II neurons are responsible for relaying deep, delocalized, often thermally associated pain commonly experienced in spinal cord injury pathologies. We analyzed dendritic spine morphometry and localization in tissue obtained from adult rats exhibiting neuropathic pain one-month following spinal cord injury. Although the total density of dendritic spines on lamina II neurons did not change after spinal cord injury, we observed an inverse relationship between the densities of thin- and mushroom-shaped spines: thin-spine density decreased while mushroom-spine density increased. These structural changes were specifically noted along dendritic branches within 150 µm from the soma, suggesting a possible adverse contribution to nociceptive circuit function. Intrathecal treatment with NSC23766, a Rac1-GTPase inhibitor, significantly reduced spinal cord injury-induced changes in both thin- and mushroom-shaped dendritic spines. Overall, these observations demonstrate that dendritic spine remodeling occurs in lamina II, regulated in part by the Rac1-signaling pathway, and suggests that structural abnormalities in this spinal cord region may also contribute to abnormal nociception after spinal cord injury.
Topics: Analysis of Variance; Animals; Antineoplastic Agents; Dendritic Spines; Disease Models, Animal; Male; Nocodazole; Posterior Horn Cells; Rats; Rats, Sprague-Dawley; Silver Staining; Spinal Cord Injuries
PubMed: 28326929
DOI: 10.1177/1744806916688016 -
Experimental Brain Research Apr 2012The amyloid precursor protein (APP) is transported in high amounts to the presynaptic endings where its function is still unknown. Several studies indicate that lack of... (Review)
Review
The amyloid precursor protein (APP) is transported in high amounts to the presynaptic endings where its function is still unknown. Several studies indicate that lack of APP or its overexpression affects the number of dendritic spines, the postsynaptic compartment of excitatory synapses. Since synapse loss has been identified as one of the most important structural correlates of cognitive decline in Alzheimer's diseases (AD), the physiological function of APP at synapses, specifically at dendritic spines, has come into focus in AD research. This review intends to give an overview of the very controversial results on APP expression on dendritic spine number in the mouse brain.
Topics: Amyloid beta-Protein Precursor; Animals; Dendritic Spines; Humans; Mice; Protein Stability; Synapses
PubMed: 22094714
DOI: 10.1007/s00221-011-2939-x -
Cellular and Molecular Life Sciences :... Dec 2017The nervous system is populated by diverse types of neurons, each of which has dendritic trees with strikingly different morphologies. These neuron-specific morphologies... (Review)
Review
The nervous system is populated by diverse types of neurons, each of which has dendritic trees with strikingly different morphologies. These neuron-specific morphologies determine how dendritic trees integrate thousands of synaptic inputs to generate different firing properties. To ensure proper neuronal function and connectivity, it is necessary that dendrite patterns are precisely controlled and coordinated with synaptic activity. Here, we summarize the molecular and cellular mechanisms that regulate the formation of cell type-specific dendrite patterns during development. We focus on different aspects of vertebrate dendrite patterning that are particularly important in determining the neuronal function; such as the shape, branching, orientation and size of the arbors as well as the development of dendritic spine protrusions that receive excitatory inputs and compartmentalize postsynaptic responses. Additionally, we briefly comment on the implications of aberrant dendritic morphology for nervous system disease.
Topics: Animals; Dendritic Spines; Humans; Nervous System Diseases; Neurons; Synaptic Potentials
PubMed: 28735442
DOI: 10.1007/s00018-017-2588-8