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Seminars in Cell & Developmental Biology May 2022Synapses are specialized sites where neurons connect and communicate with each other. Activity-dependent modification of synaptic structure and function provides a... (Review)
Review
Synapses are specialized sites where neurons connect and communicate with each other. Activity-dependent modification of synaptic structure and function provides a mechanism for learning and memory. The advent of high-resolution time-lapse imaging in conjunction with fluorescent biosensors and actuators enables researchers to monitor and manipulate the structure and function of synapses both in vitro and in vivo. This review focuses on recent imaging studies on the synaptic modification underlying learning and memory.
Topics: Dendritic Spines; Learning; Neurons; Synapses
PubMed: 34020876
DOI: 10.1016/j.semcdb.2021.05.015 -
Annual Review of Pathology May 2016Substantial progress has been made toward understanding the neuropathology, genetic origins, and epidemiology of neurodegenerative diseases, including Alzheimer's... (Review)
Review
Substantial progress has been made toward understanding the neuropathology, genetic origins, and epidemiology of neurodegenerative diseases, including Alzheimer's disease; tauopathies, such as frontotemporal dementia; α-synucleinopathies, such as Parkinson's disease or dementia with Lewy bodies; Huntington's disease; and amyotrophic lateral sclerosis with dementia, as well as prion diseases. Recent evidence has implicated dendritic spine dysfunction as an important substrate of the pathogenesis of dementia in these disorders. Dendritic spines are specialized structures, extending from the neuronal processes, on which excitatory synaptic contacts are formed, and the loss of dendritic spines correlates with the loss of synaptic function. We review the literature that has implicated direct or indirect structural alterations at dendritic spines in the pathogenesis of major neurodegenerative diseases, focusing on those that lead to dementias such as Alzheimer's, Parkinson's, and Huntington's diseases, as well as frontotemporal dementia and prion diseases. We stress the importance of in vivo studies in animal models.
Topics: Animals; Dendritic Spines; Humans; Neurodegenerative Diseases
PubMed: 26907528
DOI: 10.1146/annurev-pathol-012615-044216 -
Molecular and Cellular Neurosciences Oct 2017Dendritic spines form typical excitatory synapses in the brain and their shapes vary depending on synaptic inputs. It has been suggested that the morphological changes... (Review)
Review
Dendritic spines form typical excitatory synapses in the brain and their shapes vary depending on synaptic inputs. It has been suggested that the morphological changes of dendritic spines play an important role in synaptic plasticity. Dendritic spines contain a high concentration of actin, which has a central role in supporting cell motility, and polymerization of actin filaments (F-actin) is most likely involved in spine shape changes. Drebrin is an actin-binding protein that forms stable F-actin and is highly accumulated within dendritic spines. Drebrin has two isoforms, embryonic-type drebrin E and adult-type drebrin A, that change during development from E to A. Inhibition of drebrin A expression results in a delay of synapse formation and inhibition of postsynaptic protein accumulation, suggesting that drebrin A has an important role in spine maturation. In mature synapses, glutamate stimulation induces rapid spine-head enlargement during long-term potentiation (LTP) formation. LTP stimulation induces Ca entry through N-methyl-d-aspartate (NMDA) receptors, which causes drebrin exodus from dendritic spines. Once drebrin exits from dendritic spine heads, the dynamic actin pool increases in spine heads to facilitate F-actin polymerization. To maintain enlarged spine heads, drebrin-decorated F-actin is thought to reform within the spine heads. Thus, drebrin plays a pivotal role in spine plasticity through regulation of F-actin.
Topics: Animals; Dendrites; Dendritic Spines; Humans; Neuronal Plasticity; Neurons; Neuropeptides; Synapses
PubMed: 28161364
DOI: 10.1016/j.mcn.2017.01.004 -
Advances in Experimental Medicine and... 2017Synaptic plasticity underlies higher brain function such as learning and memory, and the actin cytoskeleton in dendritic spines composing excitatory postsynaptic sites... (Review)
Review
Synaptic plasticity underlies higher brain function such as learning and memory, and the actin cytoskeleton in dendritic spines composing excitatory postsynaptic sites plays a pivotal role in synaptic plasticity. In this chapter, we review the role of drebrin in the regulation of the actin cytoskeleton during synaptic plasticity, under long-term potentiation (LTP) and long-term depression (LTD). Dendritic spines have two F-actin pools, drebrin-decorated stable F-actin (DF-actin) and drebrin-free dynamic F-actin (FF-actin). Resting dendritic spines change their shape, but are fairly constant over time at steady state because of the presence of DF-actin. Accumulation of DF-actin is inversely regulated by the intracellular Ca concentration. However, LTP and LTD stimulation induce Ca influx through N-methyl-D-aspartate (NMDA) receptors into the potentiated spines, resulting in drebrin exodus via myosin II ATPase activation. The potentiated spines change to excited state because of the decrease in DF-actin and thus change their shape robustly. In LTP, the Ca increase via NMDA receptors soon returns to the basal level, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) expression at the postsynaptic membrane is increased. The Ca recovery and AMPAR increase coordinately induce the re-accumulation of DF-actin and change the dendritic spines from the excited state to steady state during LTP maintenance. During LTD, the prolonged intracellular Ca increase inhibits the re-accumulation of DF-actin, resulting in facilitation of AMPAR endocytosis. Because of the positive feedback loop of the AMPAR decrease and drebrin re-accumulation inhibition, the dendritic spines are instable during LTD maintenance. Taken together, we propose the presence of resilient spines at steady state and plastic spines at excited state and discuss the physiological and pathological relevance of the two-state model to synaptic plasticity.
Topics: Actin Cytoskeleton; Actins; Animals; Dendritic Spines; Neuronal Plasticity; Neurons; Neuropeptides; Synapses; Synaptic Membranes
PubMed: 28865021
DOI: 10.1007/978-4-431-56550-5_11 -
Progress in Molecular Biology and... 2015The failure of neuropathic pain to abate even years after trauma suggests that adverse changes to synaptic function must exist in a chronic pathological state in... (Review)
Review
The failure of neuropathic pain to abate even years after trauma suggests that adverse changes to synaptic function must exist in a chronic pathological state in nociceptive pathways. The chronicity of neuropathic pain therefore underscores the importance of understanding the contribution of dendritic spines--micron-sized postsynaptic structures that represent modifiable sites of synaptic contact. Historically, dendritic spines have been of great interest to the learning and memory field. More recent evidence points to the exciting implication that abnormal dendritic spine structure following disease or injury may represent a "molecular memory" for maintaining chronic pain. Dendritic spine dysgenesis in dorsal horn neurons contributes to nociceptive hyperexcitability associated with neuropathic pain, as demonstrated in multiple pain models, i.e., spinal cord injury, peripheral nerve injury, diabetic neuropathy, and thermal burn injury. Because of the relationship between dendritic spine structure and neuronal function, a thorough investigation of dendritic spine behavior in the spinal cord is a unique opportunity to better understand the mechanisms of sensory dysfunction after injury or disease. At a conceptual level, a spinal memory mechanism that engages dendritic spine remodeling would also contribute to a broad range of intractable neurological conditions. Molecules involved in regulating dendritic spine plasticity may offer novel targets for the development of effective and durable therapies for neurological disease.
Topics: Animals; Burns; Dendritic Spines; Diabetic Neuropathies; Humans; Neuralgia; Spinal Cord Injuries; Synapses
PubMed: 25744680
DOI: 10.1016/bs.pmbts.2014.12.001 -
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 -
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 -
Neuropharmacology Jan 2016IRSp53 (also known as BAIAP2) is a multi-domain scaffolding and adaptor protein that has been implicated in the regulation of membrane and actin dynamics at subcellular... (Review)
Review
IRSp53 (also known as BAIAP2) is a multi-domain scaffolding and adaptor protein that has been implicated in the regulation of membrane and actin dynamics at subcellular structures, including filopodia and lamellipodia. Accumulating evidence indicates that IRSp53 is an abundant component of the postsynaptic density at excitatory synapses and an important regulator of actin-rich dendritic spines. In addition, IRSp53 has been implicated in diverse psychiatric disorders, including autism spectrum disorders, schizophrenia, and attention deficit/hyperactivity disorder. Mice lacking IRSp53 display enhanced NMDA (N-methyl-d-aspartate) receptor function accompanied by social and cognitive deficits, which are reversed by pharmacological suppression of NMDA receptor function. These results suggest the hypothesis that defective actin/membrane modulation in IRSp53-deficient dendritic spines may lead to social and cognitive deficits through NMDA receptor dysfunction. This article is part of the Special Issue entitled 'Synaptopathy--from Biology to Therapy'.
Topics: Actin Cytoskeleton; Animals; Brain; Cell Membrane; Dendritic Spines; Humans; Mental Disorders; Mice; Nerve Tissue Proteins; Phenotype; Post-Synaptic Density; Protein Interaction Domains and Motifs; RNA, Messenger; Receptors, N-Methyl-D-Aspartate
PubMed: 26275848
DOI: 10.1016/j.neuropharm.2015.06.019 -
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 -
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