scholarly journals Completion of neuronal remodeling prompts myelination along developing motor axon branches

2021 ◽  
Vol 220 (4) ◽  
Author(s):  
Mengzhe Wang ◽  
Tatjana Kleele ◽  
Yan Xiao ◽  
Gabriela Plucinska ◽  
Petros Avramopoulos ◽  
...  
Keyword(s):  
Fine Tuning ◽  
Structural Components ◽  
Tuning Mechanism ◽  
Neuronal Remodeling ◽  
Cytoskeletal Dynamics ◽  
Axon Branch ◽  
Circuit Function ◽  
Activity Dependent ◽  
Node Formation ◽  
Delayed Myelination

Neuronal remodeling and myelination are two fundamental processes during neurodevelopment. How they influence each other remains largely unknown, even though their coordinated execution is critical for circuit function and often disrupted in neuropsychiatric disorders. It is unclear whether myelination stabilizes axon branches during remodeling or whether ongoing remodeling delays myelination. By modulating synaptic transmission, cytoskeletal dynamics, and axonal transport in mouse motor axons, we show that local axon remodeling delays myelination onset and node formation. Conversely, glial differentiation does not determine the outcome of axon remodeling. Delayed myelination is not due to a limited supply of structural components of the axon–glial unit but rather is triggered by increased transport of signaling factors that initiate myelination, such as neuregulin. Further, transport of promyelinating signals is regulated via local cytoskeletal maturation related to activity-dependent competition. Our study reveals an axon branch–specific fine-tuning mechanism that locally coordinates axon remodeling and myelination.

scholarly journals AMPA receptor inhibition by synaptically released zinc

2015 ◽  
Vol 112 (51) ◽  
pp. 15749-15754 ◽  
Author(s):  
Bopanna I. Kalappa ◽  
Charles T. Anderson ◽  
Jacob M. Goldberg ◽  
Stephen J. Lippard ◽  
Thanos Tzounopoulos
Keyword(s):  
Dorsal Cochlear Nucleus ◽  
Fine Tuning ◽  
Receptor Inhibition ◽  
Endogenous Modulator ◽  
Excitatory Neurotransmission ◽  
Zinc Levels ◽  
Zinc Inhibition ◽  
Endogenous Modulators ◽  
Activity Dependent

The vast amount of fast excitatory neurotransmission in the mammalian central nervous system is mediated by AMPA-subtype glutamate receptors (AMPARs). As a result, AMPAR-mediated synaptic transmission is implicated in nearly all aspects of brain development, function, and plasticity. Despite the central role of AMPARs in neurobiology, the fine-tuning of synaptic AMPA responses by endogenous modulators remains poorly understood. Here we provide evidence that endogenous zinc, released by single presynaptic action potentials, inhibits synaptic AMPA currents in the dorsal cochlear nucleus (DCN) and hippocampus. Exposure to loud sound reduces presynaptic zinc levels in the DCN and abolishes zinc inhibition, implicating zinc in experience-dependent AMPAR synaptic plasticity. Our results establish zinc as an activity-dependent, endogenous modulator of AMPARs that tunes fast excitatory neurotransmission and plasticity in glutamatergic synapses.

scholarly journals Coupling of L-Type Ca2+ Channels to KV7/KCNQ Channels Creates a Novel, Activity-Dependent, Homeostatic Intrinsic Plasticity

2008 ◽  
Vol 100 (4) ◽  
pp. 1897-1908 ◽  
Author(s):  
Wendy W. Wu ◽  
C. Savio Chan ◽  
D. James Surmeier ◽  
John F. Disterhoft
Keyword(s):  
Pyramidal Neurons ◽  
Firing Frequency ◽  
Fine Tuning ◽  
Membrane Excitability ◽  
Kcnq Channels ◽  
Central Neurons ◽  
Subsequent Activation ◽  
Intrinsic Plasticity ◽  
Dependent Modification ◽  
Activity Dependent

Experience-dependent modification in the electrical properties of central neurons is a form of intrinsic plasticity that occurs during development and has been observed following behavioral learning. We report a novel form of intrinsic plasticity in hippocampal CA1 pyramidal neurons mediated by the KV7/KCNQ and CaV1/L-type Ca2+ channels. Enhancing Ca2+ influx with a conditioning spike train (30 Hz, 3 s) potentiated the KV7/KCNQ channel function and led to a long-lasting, activity-dependent increase in spike frequency adaptation—a gradual reduction in the firing frequency in response to sustained excitation. These effects were abolished by specific blockers for CaV1/L-type Ca2+ channels, KV7/KCNQ channels, and protein kinase A (PKA). Considering the widespread expression of these two channel types, the influence of Ca2+ influx and subsequent activation of PKA on KV7/KCNQ channels may represent a generalized principle in fine tuning the output of central neurons that promotes stability in firing—an example of homeostatic regulation of intrinsic membrane excitability.

Functional analysis of the SUMOylation pathway in Drosophila

2008 ◽  
Vol 36 (5) ◽  
pp. 868-873 ◽  
Author(s):  
Ana Talamillo ◽  
Jonatan Sánchez ◽  
Rosa Barrio
Keyword(s):  
Functional Analysis ◽  
Fine Tuning ◽  
Model Systems ◽  
Post Translational Modification ◽  
Reversible Process ◽  
Cellular Processes ◽  
Tuning Mechanism ◽  
Sumo Conjugation

SUMOylation, a reversible process used as a ‘fine-tuning’ mechanism to regulate the role of multiple proteins, is conserved throughout evolution. This post-translational modification affects several cellular processes by the modulation of subcellular localization, activity or stability of a variety of substrates. A growing number of proteins have been identified as targets for SUMOylation, although, for many of them, the role of SUMO conjugation on their function is unknown. The use of model systems might facilitate the study of SUMOylation implications in vivo. In the present paper, we have compiled what is known about SUMOylation in Drosophila melanogaster, where the use of genetics provides new insights on SUMOylation's biological roles.

scholarly journals Myosin-II activity generates a dynamic steady state with continuous actin turnover in a minimal actin cortex

2018 ◽  
Author(s):  
Sonal ◽  
Kristina A. Ganzinger ◽  
Sven K. Vogel ◽  
Jonas Mücksch ◽  
Philipp Blumhardt ◽  
...  
Keyword(s):  
Steady State ◽  
Actin Polymerization ◽  
Myosin Ii ◽  
Fine Tuning ◽  
Cellular Functions ◽  
Actin Cortex ◽  
Actin Turnover ◽  
Cytoskeletal Dynamics

ABSTRACTDynamic reorganization of the actomyosin cytoskeleton allows a fine-tuning of cell shape that is vital to many cellular functions. It is well established that myosin-II motors generate the forces required for remodeling the cell surface by imparting contractility to actin networks. An additional, less understood, role of myosin-II in cytoskeletal dynamics is believed to be in the regulation of actin turnover; it has been proposed that myosin activity increases actin turnover in various cellular contexts, presumably by contributing to disassembly. In vitro reconstitution of actomyosin networks has confirmed the role of myosin in actin network disassembly, but factors such as diffusional constraints and the use of stabilized filaments have thus far limited the observation of myosin-assisted actin turnover in these networks. Here, we present the reconstitution of a minimal dynamic actin cortex where actin polymerization is catalyzed on the membrane in the presence of myosin-II activity. We demonstrate that myosin activity leads to disassembly and redistribution in this simplified cortex. Consequently, a new dynamic steady state emerges in which actin filaments undergo constant turnover. Our findings suggest a multi-faceted role of myosin-II in fast remodeling of the eukaryotic actin cortex.

The ability to combine multiple mRNA antigens targeting multiple pathogens simultaneously, and the robust immune responses are confirmed in several clinical studies

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Immune Responses ◽  
Clinical Studies ◽  
Large Scale ◽  
Antigen Expression ◽  
Fine Tuning ◽  
Cold Chain ◽  
Disruptive Technology ◽  
Single Shot ◽  
Structural Components ◽  
Multiple Pathogens

In the last decade, great progress has been made on mRNA vaccines. MRNA vaccines that are well-tolerated and human immunogenic, stable and can be scaled up to hundreds of millions of doses have been produced with advancements in mRNA design, lipid nanoparticles (LNPs) composition and production techniques. The ability to combine multiple mRNA antigens in the same LNP, targeting multiple pathogens simultaneously, the lack of vector immunity, and the robust immune responses confirmed in several clinical studies make mRNA vaccines a disruptive technology that could change the development of vaccines in the coming years. Moreover, as mRNA was recently employed for large-scale vaccination applications, there is still plenty of room for refining and new advances.Ad-vector-based vaccines have also become promising immunization platforms. Ad vectors' structural components can be harnessed and modified for enhanced tropism, efficient transduction, and optimal antigen expression, and the structural components of Ad vaccine vectors can be harnessed and modified for enhanced tropism, effective transduction, and optimal antigen expression. Ad vectors can be readily created and mass-produced on a commercial basis, and their potency and stability make single-shot immunizations viable without using a frozen cold chain. Ad vectors' flexibility and promise for present and future vaccination applications is evidenced by their development against many illnesses.The use of biomaterials and engineering to improve vaccine delivery control has shown promise in boosting vaccination efficiency and fine-tuning the responses induced. Taken together, these vaccine science innovations have the potential to overcome many of the shortcomings in traditional vaccination technology, and they will almost probably play a crucial part in developing future known and novel disease vaccines.

scholarly journals Rapid and sustained homeostatic control of presynaptic exocytosis at a central synapse

2019 ◽  
Vol 116 (47) ◽  
pp. 23783-23789 ◽  
Author(s):  
Igor Delvendahl ◽  
Katarzyna Kita ◽  
Martin Müller
Keyword(s):  
Time Scales ◽  
Neural Circuit ◽  
Mossy Fiber ◽  
Pool Size ◽  
Homeostatic Plasticity ◽  
Experimental Conditions ◽  
Central Synapse ◽  
Circuit Function ◽  
Vesicle Pool ◽  
Activity Dependent

Animal behavior is remarkably robust despite constant changes in neural activity. Homeostatic plasticity stabilizes central nervous system (CNS) function on time scales of hours to days. If and how CNS function is stabilized on more rapid time scales remains unknown. Here, we discovered that mossy fiber synapses in the mouse cerebellum homeostatically control synaptic efficacy within minutes after pharmacological glutamate receptor impairment. This rapid form of homeostatic plasticity is expressed presynaptically. We show that modulations of readily releasable vesicle pool size and release probability normalize synaptic strength in a hierarchical fashion upon acute pharmacological and prolonged genetic receptor perturbation. Presynaptic membrane capacitance measurements directly demonstrate regulation of vesicle pool size upon receptor impairment. Moreover, presynaptic voltage-clamp analysis revealed increased Ca2+-current density under specific experimental conditions. Thus, homeostatic modulation of presynaptic exocytosis through specific mechanisms stabilizes synaptic transmission in a CNS circuit on time scales ranging from minutes to months. Rapid presynaptic homeostatic plasticity may ensure stable neural circuit function in light of rapid activity-dependent plasticity.

Prolonged plasticity: Necessary and sufficient for language-ready brains

2008 ◽  
Vol 31 (5) ◽  
pp. 514-515 ◽  
Author(s):  
Patricia J. Brooks ◽  
Sonia Ragir
Keyword(s):  
Social Development ◽  
Social Groups ◽  
Postnatal Growth ◽  
Fine Tuning ◽  
Shared Meaning ◽  
Neural Connections ◽  
Wide Range ◽  
Necessary And Sufficient ◽  
Communal Exchange ◽  
Activity Dependent

AbstractLanguages emerge in response to the negotiation of shared meaning in social groups, where transparency of grammar is necessitated by demands of communication with relative strangers needing to consult on a wide range of topics (Ragir 2002). This communal exchange is automated and stabilized through activity-dependent fine-tuning of information-specific neural connections during postnatal growth and social development.

scholarly journals Superresolution imaging reveals activity-dependent plasticity of axon morphology linked to changes in action potential conduction velocity

2017 ◽  
Vol 114 (6) ◽  
pp. 1401-1406 ◽  
Author(s):  
Ronan Chéreau ◽  
G. Ezequiel Saraceno ◽  
Julie Angibaud ◽  
Daniel Cattaert ◽  
U. Valentin Nägerl
Keyword(s):  
Conduction Velocity ◽  
High Frequency ◽  
Information Transfer ◽  
Brain Slices ◽  
Morphological Plasticity ◽  
Time Lapse ◽  
Progressive Increase ◽  
Fine Tuning ◽  
Synaptic Boutons ◽  
Activity Dependent

Axons convey information to nearby and distant cells, and the time it takes for action potentials (APs) to reach their targets governs the timing of information transfer in neural circuits. In the unmyelinated axons of hippocampus, the conduction speed of APs depends crucially on axon diameters, which vary widely. However, it is not known whether axon diameters are dynamic and regulated by activity-dependent mechanisms. Using time-lapse superresolution microscopy in brain slices, we report that axons grow wider after high-frequency AP firing: synaptic boutons undergo a rapid enlargement, which is mostly transient, whereas axon shafts show a more delayed and progressive increase in diameter. Simulations of AP propagation incorporating these morphological dynamics predicted bidirectional effects on AP conduction speed. The predictions were confirmed by electrophysiological experiments, revealing a phase of slowed down AP conduction, which is linked to the transient enlargement of the synaptic boutons, followed by a sustained increase in conduction speed that accompanies the axon shaft widening induced by high-frequency AP firing. Taken together, our study outlines a morphological plasticity mechanism for dynamically fine-tuning AP conduction velocity, which potentially has wide implications for the temporal transfer of information in the brain.

Increase of SARS-CoV 3CL peptidase activity due to macromolecular crowding effects in the milieu composition

2010 ◽  
Vol 391 (12) ◽  
Author(s):  
Debora N. Okamoto ◽  
Lilian C.G. Oliveira ◽  
Marcia Y. Kondo ◽  
Maria H.S. Cezari ◽  
Zoltán Szeltner ◽  
...  
Keyword(s):  
Rna Virus ◽  
Antiviral Agents ◽  
Fine Tuning ◽  
Host Cells ◽  
Respiratory Syndrome Virus ◽  
Peptidase Activity ◽  
Buffer Solutions ◽  
Tuning Mechanism ◽  
Positive Strand Rna Virus ◽  
Positive Strand Rna

Abstract The 3C-like peptidase of the severe acute respiratory syndrome virus (SARS-CoV) is strictly required for viral replication, thus being a potential target for the development of antiviral agents. In contrast to monomeric picornavirus 3C peptidases, SARS-CoV 3CLpro exists in equilibrium between the monomer and dimer forms in solution, and only the dimer is proteolytically active in dilute buffer solutions. In this study, the increase of SARS-CoV 3CLpro peptidase activity in presence of kosmotropic salts and crowding agents is described. The activation followed the Hofmeister series of anions, with two orders of magnitude enhancement in the presence of Na2SO4, whereas the crowding agents polyethylene glycol and bovine serum albumin increased the hydrolytic rate up to 3 times. Kinetic determinations of the monomer dimer dissociation constant (K d) indicated that activation was a result of a more active dimer, without significant changes in K d values. The activation was found to be independent of substrate length and was derived from both k cat increase and K m decrease. The viral peptidase activation described here could be related to the crowded intracellular environment and indicates a further fine-tuning mechanism for biological control, particularly in the microenvironment of the vesicles that are induced in host cells during positive strand RNA virus infection.

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