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Experimental Cell Research Jul 2015Before fusing with the presynaptic plasma membrane to release neurotransmitter into the synaptic cleft synaptic vesicles have to be recruited to and docked at a... (Review)
Review
Before fusing with the presynaptic plasma membrane to release neurotransmitter into the synaptic cleft synaptic vesicles have to be recruited to and docked at a specialized area of the presynaptic nerve terminal, the active zone. Exocytosis of synaptic vesicles is restricted to the presynaptic active zone, which is characterized by a unique and highly interconnected set of proteins. The protein network at the active zone is integrally involved in this process and also mediates changes in release properties, for example in response to alterations in the level of neuronal network activity. In recent years the development of novel techniques has greatly advanced our understanding of the molecular identity of respective active zone components as well as of the ultrastructure of this membranous subcompartment and of the SV release machinery. Furthermore, active zones are now viewed as dynamic structures whose composition and size are correlated with synaptic efficacy. Therefore, the dynamic remodeling of the protein network at the active zone has emerged as one potential mechanism underlying acute and long-term synaptic plasticity. Here, we will discuss this recent progress and its implications for our view of the role of the AZ in synaptic function.
Topics: Adaptor Proteins, Vesicular Transport; Animals; Humans; Neurotransmitter Agents; Presynaptic Terminals; Synaptic Vesicles
PubMed: 25720549
DOI: 10.1016/j.yexcr.2015.02.011 -
Journal of Visualized Experiments : JoVE Aug 2009The nervous system transmits signals between neurons via neurotransmitter release during synaptic vesicle fusion. To observe neurotransmitter uptake and release from...
The nervous system transmits signals between neurons via neurotransmitter release during synaptic vesicle fusion. To observe neurotransmitter uptake and release from individual presynaptic terminals directly, we designed fluorescent false neurotransmitters as substrates for the synaptic vesicle monoamine transporter. Using these probes to image dopamine release in the striatum, we made several observations pertinent to synaptic plasticity. We found that the fraction of synaptic vesicles releasing neurotransmitter per stimulus was dependent on the stimulus frequency. A kinetically distinct "reserve" synaptic vesicle population was not observed under these experimental conditions. A frequency-dependent heterogeneity of presynaptic terminals was revealed that was dependent in part on D2 dopamine receptors, indicating a mechanism for frequency-dependent coding of presynaptic selection.
Topics: Animals; Benz(a)Anthracenes; Corpus Striatum; Dopamine; Fluorescent Dyes; Male; Mice; Neuronal Plasticity; Presynaptic Terminals; Receptors, Dopamine D2; Synaptic Transmission
PubMed: 19721412
DOI: 10.3791/1562 -
Journal of Alzheimer's Disease : JAD 2019It is now more than two decades since amyloid-β (Aβ), the proteolytic product of the amyloid-β protein precursor (AβPP), was first demonstrated to be a normal and... (Review)
Review
It is now more than two decades since amyloid-β (Aβ), the proteolytic product of the amyloid-β protein precursor (AβPP), was first demonstrated to be a normal and soluble product of neuronal metabolism. To date, despite a growing body of evidence suggests its regulatory role on synaptic function, the exact cellular and molecular pathways involved in Aβ-driven synaptic effects remain elusive. This review provides an overview of the mounting evidence showing Aβ-mediated effects on presynaptic functions and neurotransmitter release from axon terminals, focusing on its interaction with synaptic vesicle cycle. Indeed, Aβ peptides have been found to interact with key presynaptic scaffold proteins and kinases affecting the consequential steps of the synaptic vesicle dynamics (e.g., synaptic vesicles exocytosis, endocytosis, and trafficking). Defects in the fine-tuning of synaptic vesicle cycle by Aβ and deregulation of key molecules and kinases, which orchestrate synaptic vesicle availability, may alter synaptic homeostasis, possibly contributing to synaptic loss and cognitive decline. Elucidating the presynaptic mechanisms by which Aβ regulate synaptic transmission is fundamental for a deeper comprehension of the biology of presynaptic terminals as well as of Aβ-driven early synaptic defects occurring in prodromal stage of AD. Moreover, a better understating of Aβ involvement in cellular signal pathways may allow to set up more effective therapeutic interventions by detecting relevant molecular mechanisms, whose imbalance might ultimately lead to synaptic impairment in AD.
Topics: Amyloid beta-Peptides; Animals; Endocytosis; Exocytosis; Humans; Presynaptic Terminals; Synapses; Synaptic Vesicles
PubMed: 31561377
DOI: 10.3233/JAD-190771 -
Trends in Neurosciences Jun 2018Today, we understand peptide transmitters to be signaling molecules that modulate neural activity. However, in 1982 little was known about neuropeptides and their role... (Review)
Review
Today, we understand peptide transmitters to be signaling molecules that modulate neural activity. However, in 1982 little was known about neuropeptides and their role in neural communication. The influential 1982 paper by Jan and Jan reported definitive evidence that a presynaptically released neuropeptide evokes postsynaptic responses in an identified cholinergic synapse, thereby fueling a new era in neuroscience.
Topics: Animals; Humans; Neuropeptides; Presynaptic Terminals; Synaptic Transmission
PubMed: 29801523
DOI: 10.1016/j.tins.2018.03.013 -
Acta Biologica Hungarica 1999It is generally accepted that neurochemical transmission occurring at the synapse is the primary way of sending messages from one neuron to another. Neurotransmitters... (Review)
Review
It is generally accepted that neurochemical transmission occurring at the synapse is the primary way of sending messages from one neuron to another. Neurotransmitters released from axon terminal in a [Ca2+]0-dependent manner act transsynaptically on the postsynaptic site. The past 30 years have witnessed something of a revolution in the understanding of how neurons communicate with each other. It has been shown that the exocytotic release of transmitters from axon terminals is subject to presynaptic modulation via presynatic hetero- and auto-receptors. For example via stimulation of alpha2-adrenoceptors expressed on varicosities and coupled to G-protein the stimulation-evoked release of different transmitters can be inhibited. This review will focus on nonsynaptic interactions between axon terminals. The present data clearly show that transmitters released from axon terminals without synaptic contact play an important role in the fine tuning of communication between neurons within a neuronal circuit.
Topics: Animals; Humans; Presynaptic Terminals; Receptors, Adrenergic, alpha-2; Synaptic Transmission
PubMed: 10574448
DOI: No ID Found -
Neurotoxicology Jun 2004Low concentrations of inorganic lead ions (Pb2+) disrupt transmitter release by causing aberrant augmentation of spontaneous and suppression of evoked release. These... (Review)
Review
Low concentrations of inorganic lead ions (Pb2+) disrupt transmitter release by causing aberrant augmentation of spontaneous and suppression of evoked release. These effects result from high affinity interactions of Pb2+ with the voltage-gated calcium channels (VGCC) as well as Ca2+ binding proteins which regulate the synaptic vesicle mobilization, docking, and exocytosis processes. Augmentation of spontaneous release may involve stimulation of vesicle mobilization consequent to Pb2+ activation of CaMKII-dependent phosphorylation of synapsin I and/or stimulation of asynchronous exocytosis via direct Pb2+ activation of the putative exocytotic Ca2+-sensor protein synaptotagmin I. In addition, synergistic stimulation of PLC and DAG/Pb2+-dependent activation of PKC may enhance the secretagogue effects of Pb2+ by increasing metal sensitivity of exocytosis and/or modulating calcium channel activity. In contrast to intracellularly-mediated actions of Pb2+ resulting in augmentation of spontaneous release, the inhibition of evoked transmitter release by Pb2+ is largely attributable to extracellular block of the voltage-gated calcium channels.
Topics: Animals; Calcium Channels; Humans; Lead; Neurotransmitter Agents; Presynaptic Terminals
PubMed: 15183013
DOI: 10.1016/j.neuro.2003.09.009 -
Journal of Visualized Experiments : JoVE Oct 2014Synaptic transmission is an extremely rapid process. Action potential driven influx of Ca(2+) into the presynaptic terminal, through voltage-gated calcium channels...
Synaptic transmission is an extremely rapid process. Action potential driven influx of Ca(2+) into the presynaptic terminal, through voltage-gated calcium channels (VGCCs) located in the release face membrane, is the trigger for vesicle fusion and neurotransmitter release. Crucial to the rapidity of synaptic transmission is the spatial and temporal synchrony between the arrival of the action potential, VGCCs and the neurotransmitter release machinery. The ability to directly record Ca(2+) currents from the release face membrane of individual presynaptic terminals is imperative for a precise understanding of the relationship between presynaptic Ca(2+) and neurotransmitter release. Access to the presynaptic release face membrane for electrophysiological recording is not available in most preparations and presynaptic Ca(2+) entry has been characterized using imaging techniques and macroscopic current measurements--techniques that do not have sufficient temporal resolution to visualize Ca(2+) entry. The characterization of VGCCs directly at single presynaptic terminals has not been possible in central synapses and has thus far been successfully achieved only in the calyx-type synapse of the chick ciliary ganglion and in rat calyces. We have successfully addressed this problem in the giant reticulospinal synapse of the lamprey spinal cord by developing an acutely dissociated preparation of the spinal cord that yields isolated reticulospinal axons with functional presynaptic terminals devoid of postsynaptic structures. We can fluorescently label and identify individual presynaptic terminals and target them for recording. Using this preparation, we have characterized VGCCs directly at the release face of individual presynaptic terminals using immunohistochemistry and electrophysiology approaches. Ca(2+) currents have been recorded directly at the release face membrane of individual presynaptic terminals, the first such recording to be carried out at central synapses.
Topics: Animals; Axons; Calcium; Calcium Channels; Electrophysiological Phenomena; Lampreys; Presynaptic Terminals; Spinal Cord
PubMed: 25350679
DOI: 10.3791/51925 -
Current Opinion in Neurobiology Jun 2023Do dendritic spines, which comprise the postsynaptic component of most excitatory synapses, exist only for their structural dynamics, receptor trafficking, and chemical... (Review)
Review
Do dendritic spines, which comprise the postsynaptic component of most excitatory synapses, exist only for their structural dynamics, receptor trafficking, and chemical and electrical compartmentation? The answer is no. Simultaneous investigation of both spine and presynaptic terminals has recently revealed a novel feature of spine synapses. Spine enlargement pushes the presynaptic terminals with muscle-like force and augments the evoked glutamate release for up to 20 min. We now summarize the evidence that such mechanical transmission shares critical features in common with short-term potentiation (STP) and may represent the cellular basis of short-term and working memory. Thus, spine synapses produce the force of learning to leave structural traces for both short and long-term memories.
Topics: Memory, Short-Term; Synapses; Presynaptic Terminals; Dendritic Spines; Hippocampus; Neuronal Plasticity
PubMed: 36931116
DOI: 10.1016/j.conb.2023.102706 -
Current Opinion in Neurobiology Jun 2000The presynaptic cytoskeletal matrix (cytomatrix) assembled at active zones has been implicated in defining neurotransmitter release sites. Munc13, Rim, Bassoon and... (Review)
Review
The presynaptic cytoskeletal matrix (cytomatrix) assembled at active zones has been implicated in defining neurotransmitter release sites. Munc13, Rim, Bassoon and Piccolo/Aczonin are recently identified presynaptic cytomatrix proteins. These multidomain proteins are thought to organize the exocytotic and endocytotic machinery precisely at active zones.
Topics: Animals; Endocytosis; Exocytosis; Neurons; Presynaptic Terminals
PubMed: 10851173
DOI: 10.1016/s0959-4388(00)00093-3 -
Annual Review of Neuroscience 2003The chemical synapse is a specialized intercellular junction that operates nearly autonomously to allow rapid, specific, and local communication between neurons.... (Review)
Review
The chemical synapse is a specialized intercellular junction that operates nearly autonomously to allow rapid, specific, and local communication between neurons. Focusing our attention on the presynaptic terminal, we review the current understanding of how synaptic morphology is maintained and then the mechanisms in synaptic vesicle exocytosis and recycling.
Topics: Animals; Cell Adhesion; Cells, Cultured; Endocytosis; Exocytosis; Neuronal Plasticity; Presynaptic Terminals; Synaptic Vesicles; Transport Vesicles
PubMed: 14527272
DOI: 10.1146/annurev.neuro.26.041002.131445