Activity-Dependent Synaptic Competition at Mammalian Neuromuscular Junctions

Physiology ◽  
2004 ◽  
Vol 19 (3) ◽  
pp. 85-91 ◽  
Author(s):  
Mario Buffelli ◽  
Giuseppe Busetto ◽  
Carlo Bidoia ◽  
Morgana Favero ◽  
Alberto Cangiano
Keyword(s):  
Central Nervous System ◽  
Developmental Process ◽  
Neuromuscular Junctions ◽  
Neuromuscular Synapse ◽  
Epigenetic Mechanisms ◽  
Synapse Elimination ◽  
Neural Connections ◽  
Synaptic Competition ◽  
Activity Dependent

Synapse elimination is a widespread developmental process in the peripheral and central nervous system that brings about refinement of neural connections through epigenetic mechanisms. Here we describe recent advances concerning the role of the pattern of motoneuronal firing, synchronous or asynchronous, in neuromuscular synapse elimination.

scholarly journals Postsynaptic regulation of synaptic plasticity by synaptotagmin 4 requires both C2 domains

2009 ◽  
Vol 187 (2) ◽  
pp. 295-310 ◽  
Author(s):  
Cynthia F. Barber ◽  
Ramon A. Jorquera ◽  
Jan E. Melom ◽  
J. Troy Littleton
Keyword(s):  
Synaptic Plasticity ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Neuromuscular Junctions ◽  
Vesicle Fusion ◽  
Synaptic Growth ◽  
Synaptotagmin 1 ◽  
Presynaptic Vesicle ◽  
Activity Dependent

Ca2+ influx into synaptic compartments during activity is a key mediator of neuronal plasticity. Although the role of presynaptic Ca2+ in triggering vesicle fusion though the Ca2+ sensor synaptotagmin 1 (Syt 1) is established, molecular mechanisms that underlie responses to postsynaptic Ca2+ influx remain unclear. In this study, we demonstrate that fusion-competent Syt 4 vesicles localize postsynaptically at both neuromuscular junctions (NMJs) and central nervous system synapses in Drosophila melanogaster. Syt 4 messenger RNA and protein expression are strongly regulated by neuronal activity, whereas altered levels of postsynaptic Syt 4 modify synaptic growth and presynaptic release properties. Syt 4 is required for known forms of activity-dependent structural plasticity at NMJs. Synaptic proliferation and retrograde signaling mediated by Syt 4 requires functional C2A and C2B Ca2+–binding sites, as well as serine 284, an evolutionarily conserved substitution for a key Ca2+-binding aspartic acid found in other synaptotagmins. These data suggest that Syt 4 regulates activity-dependent release of postsynaptic retrograde signals that promote synaptic plasticity, similar to the role of Syt 1 as a Ca2+ sensor for presynaptic vesicle fusion.

scholarly journals Role of Connexins 30, 36, and 43 in Brain Tumors, Neurodegenerative Diseases, and Neuroprotection

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 846 ◽  
Author(s):  
Oscar F. Sánchez ◽  
Andrea V. Rodríguez ◽  
José M. Velasco-España ◽  
Laura C. Murillo ◽  
Jhon-Jairo Sutachan ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Posttranslational Modifications ◽  
Cell Communication ◽  
Normal Function ◽  
Epigenetic Mechanisms ◽  
Communication Processes ◽  
The Central Nervous System

Gap junction (GJ) channels and their connexins (Cxs) are complex proteins that have essential functions in cell communication processes in the central nervous system (CNS). Neurons, astrocytes, oligodendrocytes, and microglial cells express an extraordinary repertory of Cxs that are important for cell to cell communication and diffusion of metabolites, ions, neurotransmitters, and gliotransmitters. GJs and Cxs not only contribute to the normal function of the CNS but also the pathological progress of several diseases, such as cancer and neurodegenerative diseases. Besides, they have important roles in mediating neuroprotection by internal or external molecules. However, regulation of Cx expression by epigenetic mechanisms has not been fully elucidated. In this review, we provide an overview of the known mechanisms that regulate the expression of the most abundant Cxs in the central nervous system, Cx30, Cx36, and Cx43, and their role in brain cancer, CNS disorders, and neuroprotection. Initially, we focus on describing the Cx gene structure and how this is regulated by epigenetic mechanisms. Then, the posttranslational modifications that mediate the activity and stability of Cxs are reviewed. Finally, the role of GJs and Cxs in glioblastoma, Alzheimer’s, Parkinson’s, and Huntington’s diseases, and neuroprotection are analyzed with the aim of shedding light in the possibility of using Cx regulators as potential therapeutic molecules.

scholarly journals Transcriptional control of parallel-acting pathways that remove discrete presynaptic proteins in remodeling neurons

2020 ◽  
Author(s):  
Tyne W. Miller-Fleming ◽  
Andrea Cuentas-Condori ◽  
Laura Manning ◽  
Sierra Palumbos ◽  
Janet E. Richmond ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Transcriptional Control ◽  
Developmental Pathways ◽  
Synapse Elimination ◽  
C Elegans ◽  
Synaptic Vesicle Fusion ◽  
Activity Dependent ◽  
Presynaptic Proteins ◽  
Dependent Mechanism

ABSTRACTSynapses are actively dismantled to mediate circuit refinement, but the developmental pathways that regulate synaptic disassembly are largely unknown. We have previously shown that the epithelial sodium channel UNC-8 triggers an activity-dependent mechanism that drives the removal of presynaptic proteins liprin-α/SYD-2, Synaptobrevin/SNB-1, RAB-3 and Endophilin/UNC-57 in remodeling GABAergic neurons in C. elegans (Miller-Fleming et al., 2016). Here, we report that the transcription factor Iroquois/IRX-1 regulates UNC-8 expression as well as an additional pathway, independent of UNC-8, that functions in parallel to dismantle functional presynaptic terminals. We show that the additional IRX-1-regulated pathway is selectively required for the removal of the presynaptic proteins, Munc13/UNC-13 and ELKS, which normally mediate synaptic vesicle fusion and neurotransmitter release. Our findings are notable because they highlight the key role of transcriptional regulation in synapse elimination and reveal parallel-acting pathways that orchestrate synaptic disassembly by removing specific active zone proteins.

scholarly journals Covering the Role of PGC-1α in the Central Nervous System

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 111
Author(s):  
Zuzanna Kuczynska ◽  
Erkan Metin ◽  
Michal Liput ◽  
Leonora Buzanska
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuromuscular Junctions ◽  
Deep Understanding ◽  
Cell Types ◽  
Postnatal Life ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Central Nervous System

The peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a well-known transcriptional coactivator involved in mitochondrial biogenesis. PGC-1α is implicated in the pathophysiology of many neurodegenerative disorders; therefore, a deep understanding of its functioning in the central nervous system may lead to the development of new therapeutic strategies. The central nervous system (CNS)-specific isoforms of PGC-1α have been recently identified, and many functions of PGC-1α are assigned to the particular cell types of the central nervous system. In the mice CNS, deficiency of PGC-1α disturbed viability and functioning of interneurons and dopaminergic neurons, followed by alterations in inhibitory signaling and behavioral dysfunction. Furthermore, in the ALS rodent model, PGC-1α protects upper motoneurons from neurodegeneration. PGC-1α is engaged in the generation of neuromuscular junctions by lower motoneurons, protection of photoreceptors, and reduction in oxidative stress in sensory neurons. Furthermore, in the glial cells, PGC-1α is essential for the maturation and proliferation of astrocytes, myelination by oligodendrocytes, and mitophagy and autophagy of microglia. PGC-1α is also necessary for synaptogenesis in the developing brain and the generation and maintenance of synapses in postnatal life. This review provides an outlook of recent studies on the role of PGC-1α in various cells in the central nervous system.

scholarly journals Myelin in the Central Nervous System: Structure, Function, and Pathology

2019 ◽  
Vol 99 (3) ◽  
pp. 1381-1431 ◽  
Author(s):  
Christine Stadelmann ◽  
Sebastian Timmler ◽  
Alonso Barrantes-Freer ◽  
Mikael Simons
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nerve Conduction ◽  
Active Role ◽  
Acute Disseminated Encephalomyelitis ◽  
System Structure ◽  
The Central Nervous System ◽  
Relationship Of ◽  
Activity Dependent

Oligodendrocytes generate multiple layers of myelin membrane around axons of the central nervous system to enable fast and efficient nerve conduction. Until recently, saltatory nerve conduction was considered the only purpose of myelin, but it is now clear that myelin has more functions. In fact, myelinating oligodendrocytes are embedded in a vast network of interconnected glial and neuronal cells, and increasing evidence supports an active role of oligodendrocytes within this assembly, for example, by providing metabolic support to neurons, by regulating ion and water homeostasis, and by adapting to activity-dependent neuronal signals. The molecular complexity governing these interactions requires an in-depth molecular understanding of how oligodendrocytes and axons interact and how they generate, maintain, and remodel their myelin sheaths. This review deals with the biology of myelin, the expanded relationship of myelin with its underlying axons and the neighboring cells, and its disturbances in various diseases such as multiple sclerosis, acute disseminated encephalomyelitis, and neuromyelitis optica spectrum disorders. Furthermore, we will highlight how specific interactions between astrocytes, oligodendrocytes, and microglia contribute to demyelination in hereditary white matter pathologies.

scholarly journals Neuronal Activity-Dependent Activation of Astroglial Calcineurin in Mouse Primary Hippocampal Cultures

2018 ◽  
Vol 19 (10) ◽  
pp. 2997 ◽  
Author(s):  
Dmitry Lim ◽  
Lisa Mapelli ◽  
Pier Luigi Canonico ◽  
Francesco Moccia ◽  
Armando A. Genazzani
Keyword(s):  
Central Nervous System ◽  
Neuronal Activity ◽  
Calcium Imaging ◽  
Protein Phosphatase ◽  
Lentiviral Vector ◽  
Calcium Signals ◽  
Hippocampal Cultures ◽  
Activity Dependent ◽  
Proof Of Principle

Astrocytes respond to neuronal activity by generating calcium signals which are implicated in the regulation of astroglial housekeeping functions and/or in modulation of synaptic transmission. We hypothesized that activity-induced calcium signals in astrocytes may activate calcineurin (CaN), a calcium/calmodulin-regulated protein phosphatase, implicated in neuropathology, but whose role in astroglial physiology remains unclear. We used a lentiviral vector expressing NFAT-EYFP (NY) fluorescent calcineurin sensor and a chemical protocol of LTP induction (cLTP) to show that, in mixed neuron-astrocytic hippocampal cultures, cLTP induced robust NY translocation into astrocyte nuclei and, hence, CaN activation. NY translocation was abolished by the CaN inhibitor FK506, and was not observed in pure astroglial cultures. Using Fura-2 single cell calcium imaging, we found sustained Ca2+ elevations in juxtaneuronal, but not distal, astrocytes. Pharmacological analysis revealed that both the Ca2+ signals and the nuclear NY translocation in astrocytes required NMDA and mGluR5 receptors and depended on extracellular Ca2+ entry via a store-operated mechanism. Our results provide a proof of principle that calcineurin in astrocytes may be activated in response to neuronal activity, thereby delineating a framework for investigating the role of astroglial CaN in the physiology of central nervous system.

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