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The Journal of Cell Biology Aug 2019The trans-synaptic cell adhesion molecule neurexin regulates synaptic functions but its high-resolution subcellular localization and dynamics were unknown. Trotter et...
The trans-synaptic cell adhesion molecule neurexin regulates synaptic functions but its high-resolution subcellular localization and dynamics were unknown. Trotter et al. (2019. https://doi.org/10.1083/jcb.201812076) describe previously unrecognized nanoscale clusters of neurexin-1 in presynaptic terminals and their regulation by ADAM10-mediated proteolysis.
Topics: Presynaptic Terminals
PubMed: 31332023
DOI: 10.1083/jcb.201907074 -
Experimental Cell Research Jul 2015Actin is the most abundant cytoskeletal protein in presynaptic terminals as well as in postsynaptic dendritic spines of central excitatory synapses. While the relevance... (Review)
Review
Actin is the most abundant cytoskeletal protein in presynaptic terminals as well as in postsynaptic dendritic spines of central excitatory synapses. While the relevance of actin dynamics for postsynaptic plasticity, for instance activity-induced changes in dendritic spine morphology and synaptic glutamate receptor mobility, is well-documented, only little is known about its function and regulatory mechanisms in presynaptic terminals. Moreover, studies on presynaptic actin dynamics have often been inconsistent, suggesting that actin has diverse presynaptic functions, varying likely between specific types of excitatory synapses and/or their activity states. In this review, we will summarize and discuss the function and upstream regulatory mechanisms of the actin cytoskeleton in presynaptic terminals, focusing on excitatory synapses of the mammalian central nervous system. Due to length restrictions we will mainly concentrate on new insights into actin's presynaptic function that have been gained by cell biological and mouse genetic approaches since the excellent 2008 review by Cingolani and Goda.
Topics: Actin Cytoskeleton; Animals; Endocytosis; Exocytosis; Humans; Presynaptic Terminals; Synaptic Transmission; Synaptic Vesicles
PubMed: 25579398
DOI: 10.1016/j.yexcr.2014.12.020 -
Neurochemistry International Jan 2008The discovery that the cytoplasmic membrane of presynaptic nerve terminals possess receptors that modulates release of neurotransmitters was made 35 years ago. This new... (Review)
Review
The discovery that the cytoplasmic membrane of presynaptic nerve terminals possess receptors that modulates release of neurotransmitters was made 35 years ago. This new concept represents a clear departure from the traditional view that neuronal communication was unidirectional, i.e. from the nerve terminal to the postsynaptic receptor, because the transfer of information via presynaptic receptors occurs in the opposite direction: from the synaptic cleft to the nerve terminals which release the neurotransmitter. Presynaptic release-modulating autoreceptors and heteroreceptors represent suitable targets for pharmacological intervention by exogenous compounds acting as agonists, partial agonists or antagonists. Such compounds may be of therapeutic value by influencing transmitter release presynaptically, and having fewer side effects than the well-established approach of using agonists or antagonist drugs to stimulate or block postsynaptic receptors.
Topics: Animals; Humans; Neurotransmitter Agents; Presynaptic Terminals; Signal Transduction; Synapses
PubMed: 17583385
DOI: 10.1016/j.neuint.2007.04.031 -
Nature Neuroscience Mar 2020Emerging evidence indicates that liquid-liquid phase separation, the formation of a condensed molecular assembly within another diluted aqueous solution, is a means for... (Review)
Review
Emerging evidence indicates that liquid-liquid phase separation, the formation of a condensed molecular assembly within another diluted aqueous solution, is a means for cells to organize highly condensed biological assemblies (also known as biological condensates or membraneless compartments) with very broad functions and regulatory properties in different subcellular regions. Molecular machineries dictating synaptic transmissions in both presynaptic boutons and postsynaptic densities of neuronal synapses may be such biological condensates. Here we review recent developments showing how phase separation can build dense synaptic molecular clusters, highlight unique features of such condensed clusters in the context of synaptic development and signaling, discuss how aberrant phase-separation-mediated synaptic assembly formation may contribute to dysfunctional signaling in psychiatric disorders, and present some challenges and opportunities of phase separation in synaptic biology.
Topics: Animals; Humans; Post-Synaptic Density; Presynaptic Terminals; Synapses; Synaptic Transmission
PubMed: 32015539
DOI: 10.1038/s41593-019-0579-9 -
Cold Spring Harbor Perspectives in... Jul 2012Different types of synapses are specialized to interpret spike trains in their own way by virtue of the complement of short-term synaptic plasticity mechanisms they... (Review)
Review
Different types of synapses are specialized to interpret spike trains in their own way by virtue of the complement of short-term synaptic plasticity mechanisms they possess. Numerous types of short-term, use-dependent synaptic plasticity regulate neurotransmitter release. Short-term depression is prominent after a single conditioning stimulus and recovers in seconds. Sustained presynaptic activation can result in more profound depression that recovers more slowly. An enhancement of release known as facilitation is prominent after single conditioning stimuli and lasts for hundreds of milliseconds. Finally, tetanic activation can enhance synaptic strength for tens of seconds to minutes through processes known as augmentation and posttetantic potentiation. Progress in clarifying the properties, mechanisms, and functional roles of these forms of short-term plasticity is reviewed here.
Topics: Animals; Humans; Neuronal Plasticity; Presynaptic Terminals
PubMed: 22751149
DOI: 10.1101/cshperspect.a005702 -
Current Opinion in Neurobiology Oct 2001Understanding the detailed molecular events that support chemical synaptic transmission requires high-resolution methods that provide quantitative information combined... (Review)
Review
Understanding the detailed molecular events that support chemical synaptic transmission requires high-resolution methods that provide quantitative information combined with molecular specificity. In recent years, many new technological approaches, including genetically encoded fluorescent indicators, ultra-thin sectioning, and live-cell imaging have been brought to bear on understanding the cell biology and physiology of presynaptic terminals.
Topics: Animals; Fluorescent Dyes; Humans; Image Processing, Computer-Assisted; Neurons; Presynaptic Terminals; Pyridinium Compounds; Quaternary Ammonium Compounds; Synaptic Transmission; Synaptic Vesicles
PubMed: 11595486
DOI: 10.1016/s0959-4388(00)00247-6 -
Neuron Oct 2001The release of neurotransmitter from nerve terminals occurs at a specialized region of the presynaptic plasma membrane called the active zone. A dense matrix of proteins... (Review)
Review
The release of neurotransmitter from nerve terminals occurs at a specialized region of the presynaptic plasma membrane called the active zone. A dense matrix of proteins associated with the active zone, called the presynaptic web, is thought to play a fundamental role in defining these neurotransmitter release sites. In this issue of Neuron, Phillips et al. have identified conditions for the biochemical purification of the presynaptic web and show that the web is comprised of proteins involved in the docking, fusion, and recycling of synaptic vesicles.
Topics: Animals; Presynaptic Terminals; Synaptic Vesicles
PubMed: 11604132
DOI: 10.1016/s0896-6273(01)00458-5 -
Current Opinion in Structural Biology Feb 2019Neurotransmitter release at the presynaptic terminal is one of the fundamental processes in neuronal communication. It is a complex process comprising signaling pathways... (Review)
Review
Neurotransmitter release at the presynaptic terminal is one of the fundamental processes in neuronal communication. It is a complex process comprising signaling pathways that exert a precise spatio-temporal coordination to prepare and bring synaptic vesicles to exocytosis. While many molecular components involved have been identified, their direct observation at different stages of the neurotransmitter release is lacking. Three-dimensional imaging by electron tomography provided remarkable views of the synaptic vesicles and the cytomatrix. Imaging fully hydrated, vitrified samples allowed a direct visualization, precise localization and a quantitative characterization of pleomorphic synaptic vesicle-bound complexes in situ, as well as the elucidation of their function in the neurotransmitter release.
Topics: Animals; Cryoelectron Microscopy; Neurotransmitter Agents; Presynaptic Terminals
PubMed: 30925443
DOI: 10.1016/j.sbi.2019.01.008 -
Reviews in the Neurosciences Jan 2016Mechanisms for maintenance of the extracellular level of glutamate in brain tissue and its regulation still remain almost unclear, and criticism of the current paradigm... (Review)
Review
Mechanisms for maintenance of the extracellular level of glutamate in brain tissue and its regulation still remain almost unclear, and criticism of the current paradigm of glutamate transport and homeostasis has recently appeared. The main premise for this study is the existence of a definite and non-negligible concentration of ambient glutamate between the episodes of exocytotic release in our experiments with rat brain nerve terminals (synaptosomes), despite the existence of a very potent Na+-dependent glutamate uptake. Glutamate transporter reversal is considered as the main mechanisms of glutamate release under special conditions of energy deprivation, hypoxia, hypoglycemia, brain trauma, and stroke, underlying an increase in the ambient glutamate concentration and development of excitotoxicity. In the present study, a new vision on transporter-mediated release of glutamate as one of the main mechanisms involved in the maintenance of definite concentration of ambient glutamate under normal energetical status of nerve terminals is forwarded. It has been suggested that glutamate transporters act effectively in outward direction in a non-pathological manner, and this process is thermodynamically synchronized with uptake and provides effective outward glutamate current, thereby establishing and maintaining permanent and dynamic glutamatein/glutamate(out) gradient and turnover across the plasma membrane. In this context, non-transporter tonic glutamate release by diffusion, spontaneous exocytosis, cystine-glutamate exchanger, and leakage through anion channels can be considered as a permanently added 'new' exogenous substrate using two-substrate kinetic model calculations. Permanent glutamate turnover is of value for tonic activation of post/presynaptic glutamate receptors, long-term potentiation, memory formation, etc. Counterarguments against this mechanism are also considered.
Topics: Amino Acid Transport System X-AG; Animals; Exocytosis; Glutamic Acid; Humans; Presynaptic Terminals; Synaptic Transmission
PubMed: 26352200
DOI: 10.1515/revneuro-2015-0023 -
Neuron Jan 2010Learning and memory are fundamental brain functions affected by dietary and environmental factors. Here, we show that increasing brain magnesium using a newly developed... (Comparative Study)
Comparative Study
Learning and memory are fundamental brain functions affected by dietary and environmental factors. Here, we show that increasing brain magnesium using a newly developed magnesium compound (magnesium-L-threonate, MgT) leads to the enhancement of learning abilities, working memory, and short- and long-term memory in rats. The pattern completion ability was also improved in aged rats. MgT-treated rats had higher density of synaptophysin-/synaptobrevin-positive puncta in DG and CA1 subregions of hippocampus that were correlated with memory improvement. Functionally, magnesium increased the number of functional presynaptic release sites, while it reduced their release probability. The resultant synaptic reconfiguration enabled selective enhancement of synaptic transmission for burst inputs. Coupled with concurrent upregulation of NR2B-containing NMDA receptors and its downstream signaling, synaptic plasticity induced by correlated inputs was enhanced. Our findings suggest that an increase in brain magnesium enhances both short-term synaptic facilitation and long-term potentiation and improves learning and memory functions.
Topics: Age Factors; Animals; Brain; Brain Chemistry; Learning; Magnesium; Male; Memory; Presynaptic Terminals; Rats; Rats, Sprague-Dawley
PubMed: 20152124
DOI: 10.1016/j.neuron.2009.12.026