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International Journal of Molecular... Dec 2020An action potential (AP) triggers neurotransmitter release from synaptic vesicles (SVs) docking to a specialized release site of presynaptic plasma membrane, the active... (Review)
Review
An action potential (AP) triggers neurotransmitter release from synaptic vesicles (SVs) docking to a specialized release site of presynaptic plasma membrane, the active zone (AZ). The AP simultaneously controls the release site replenishment with SV for sustainable synaptic transmission in response to incoming neuronal signals. Although many studies have suggested that the replenishment time is relatively slow, recent studies exploring high speed resolution have revealed SV dynamics with milliseconds timescale after an AP. Accurate regulation is conferred by proteins sensing Ca entering through voltage-gated Ca channels opened by an AP. This review summarizes how millisecond Ca dynamics activate multiple protein cascades for control of the release site replenishment with release-ready SVs that underlie presynaptic short-term plasticity.
Topics: Animals; Humans; Neuronal Plasticity; Neurotransmitter Agents; Presynaptic Terminals; Synaptic Transmission
PubMed: 33396919
DOI: 10.3390/ijms22010327 -
ELife Apr 2023Control of neurotransmission efficacy is central to theories of how the brain computes and stores information. Presynaptic G-protein coupled receptors (GPCRs) are...
Control of neurotransmission efficacy is central to theories of how the brain computes and stores information. Presynaptic G-protein coupled receptors (GPCRs) are critical in this problem as they locally influence synaptic strength and can operate on a wide range of time scales. Among the mechanisms by which GPCRs impact neurotransmission is by inhibiting voltage-gated calcium (Ca) influx in the active zone. Here, using quantitative analysis of both single bouton Ca influx and exocytosis, we uncovered an unexpected non-linear relationship between the magnitude of action potential driven Ca influx and the concentration of external Ca ([Ca]). We find that this unexpected relationship is leveraged by GPCR signaling when operating at the nominal physiological set point for [Ca], 1.2 mM, to achieve complete silencing of nerve terminals. These data imply that the information throughput in neural circuits can be readily modulated in an all-or-none fashion at the single synapse level when operating at the physiological set point.
Topics: Synapses; Presynaptic Terminals; Synaptic Transmission; Action Potentials; gamma-Aminobutyric Acid; Calcium
PubMed: 37014052
DOI: 10.7554/eLife.83530 -
Current Opinion in Neurobiology Aug 2019Ion channels are microscopic pore proteins in the membrane that open and close in response to chemical and electrical stimuli. This simple concept underlies rapid... (Review)
Review
Ion channels are microscopic pore proteins in the membrane that open and close in response to chemical and electrical stimuli. This simple concept underlies rapid electrical signaling in the brain as well as several important aspects of neural plasticity. Although the soma accounts for less than 1% of many neurons by membrane area, it has been the major site of measuring ion channel function. However, the axon is one of the longest processes found in cellular biology and hosts a multitude of critical signaling functions in the brain. Not only does the axon initiate and rapidly propagate action potentials (APs) across the brain but it also forms the presynaptic terminals that convert these electrical inputs into chemical outputs. Here, we review recent advances in the physiological role of ion channels within the diverse landscape of the axon and presynaptic terminals.
Topics: Action Potentials; Axons; Ion Channels; Neurons; Presynaptic Terminals
PubMed: 30784979
DOI: 10.1016/j.conb.2019.01.020 -
Neuron Jun 2021Reliable optogenetic tools for sustained, projection-specific presynaptic silencing have been elusive. Recently in Neuron, Mahn et al. (2021) and Copits et al. (2021)...
Reliable optogenetic tools for sustained, projection-specific presynaptic silencing have been elusive. Recently in Neuron, Mahn et al. (2021) and Copits et al. (2021) describe how the light-activated inhibitory GPCRs eOPN3 and PPO can be used to reversibly suppress synaptic transmission in mice.
Topics: Animals; Culicidae; Mice; Neurotransmitter Agents; Optogenetics; Presynaptic Terminals; Rhodopsin; Synaptic Transmission
PubMed: 34081915
DOI: 10.1016/j.neuron.2021.05.015 -
Purinergic Signalling Jun 2024Over the last decades, since the discovery of ATP as a transmitter, accumulating evidence has been reported about the role of this nucleotide and purinergic receptors,... (Review)
Review
Over the last decades, since the discovery of ATP as a transmitter, accumulating evidence has been reported about the role of this nucleotide and purinergic receptors, in particular P2X7 receptors, in the modulation of synaptic strength and plasticity. Purinergic signaling has emerged as a crucial player in orchestrating the molecular interaction between the components of the tripartite synapse, and much progress has been made in how this neuron-glia interaction impacts neuronal physiology under basal and pathological conditions. On the other hand, pannexin1 hemichannels, which are functionally linked to P2X7 receptors, have appeared more recently as important modulators of excitatory synaptic function and plasticity under diverse contexts. In this review, we will discuss the contribution of ATP, P2X7 receptors, and pannexin hemichannels to the modulation of presynaptic strength and its impact on motor function, sensory processing, synaptic plasticity, and neuroglial communication, with special focus on the P2X7 receptor/pannexin hemichannel interplay. We also address major hypotheses about the role of this interaction in physiological and pathological circumstances.
Topics: Receptors, Purinergic P2X7; Connexins; Humans; Animals; Synaptic Transmission; Nerve Tissue Proteins; Neuronal Plasticity; Adenosine Triphosphate; Presynaptic Terminals
PubMed: 37713157
DOI: 10.1007/s11302-023-09965-8 -
The Neuroscientist : a Review Journal... Oct 2019Nervous system communication relies on neurotransmitter release for synaptic transmission between neurons. Neurotransmitter is contained within vesicles in presynaptic... (Review)
Review
Nervous system communication relies on neurotransmitter release for synaptic transmission between neurons. Neurotransmitter is contained within vesicles in presynaptic terminals and intraterminal calcium governs the fundamental step of their release into the synaptic cleft. Despite a common dependence on calcium, synaptic transmission and its modulation varies highly across the nervous system. The precise mechanisms that underlie this heterogeneity, however, remain unclear. The present review highlights recent data that reveal vesicles sourced from separate pools define discrete modes of release. A rich diversity of regulatory machinery may further distinguish the different forms of vesicle release, including presynaptic proteins involved in trafficking, alignment, and exocytosis. These multiple vesicle release mechanisms and vesicle pools likely depend on the arrangement of vesicles in relation to specific calcium entry pathways that create compartmentalized spheres of calcium influence (i.e., domains). This diversity permits release specialization. This review details examples of how individual neurons rely on multiple calcium sources and unique regulatory schemes to provide differential release and discrete modulation of neurotransmitter release from specific vesicle pools-as part of network signal integration.
Topics: Animals; Calcium Signaling; Exocytosis; Glutamic Acid; Humans; Presynaptic Terminals; Synaptic Transmission; Synaptic Vesicles
PubMed: 31375041
DOI: 10.1177/1073858419863771 -
Frontiers in Neural Circuits 2020Excitatory synapses in the mammalian cortex are highly diverse, both in terms of their structure and function. However, relationships between synaptic features indicate... (Review)
Review
Excitatory synapses in the mammalian cortex are highly diverse, both in terms of their structure and function. However, relationships between synaptic features indicate they are highly coordinated entities. Imaging techniques, that enable physiology at the resolution of individual synapses to be investigated, have allowed the presynaptic activity level of the synapse to be related to postsynaptic function. This approach has revealed that neuronal activity induces the pre- and post-synapse to be functionally correlated and that subsets of synapses are more susceptible to certain forms of synaptic plasticity. As presynaptic function is often examined in isolation from postsynaptic properties, the effect it has on the post-synapse is not fully understood. However, since postsynaptic receptors at excitatory synapses respond to release of glutamate, it follows that they may be differentially regulated depending on the frequency of its release. Therefore, examining postsynaptic properties in the context of presynaptic function may be a useful way to approach a broad range of questions on synaptic physiology. In this review, we focus on how optophysiology tools have been utilized to study relationships between the pre- and the post-synapse. Multiple imaging techniques have revealed correlations in synaptic properties from the submicron to the dendritic level. Optical tools together with advanced imaging techniques are ideally suited to illuminate this area further, due to the spatial resolution and control they allow.
Topics: Animals; Brain; Brain-Derived Neurotrophic Factor; Humans; Neuronal Plasticity; Presynaptic Terminals; Receptors, AMPA; Synapses; Synaptic Potentials; Synaptic Transmission
PubMed: 32308573
DOI: 10.3389/fncir.2020.00009 -
Science (New York, N.Y.) Mar 2024The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the trisynaptic... (Review)
Review
The hippocampal mossy fiber synapse, formed between axons of dentate gyrus granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the trisynaptic circuitry of the hippocampus. Because of its comparatively large size, this synapse is accessible to direct presynaptic recording, allowing a rigorous investigation of the biophysical mechanisms of synaptic transmission and plasticity. Furthermore, because of its placement in the very center of the hippocampal memory circuit, this synapse seems to be critically involved in several higher network functions, such as learning, memory, pattern separation, and pattern completion. Recent work based on new technologies in both nanoanatomy and nanophysiology, including presynaptic patch-clamp recording, paired recording, super-resolution light microscopy, and freeze-fracture and "flash-and-freeze" electron microscopy, has provided new insights into the structure, biophysics, and network function of this intriguing synapse. This brings us one step closer to answering a fundamental question in neuroscience: how basic synaptic properties shape higher network computations.
Topics: Mossy Fibers, Hippocampal; Presynaptic Terminals; Synaptic Transmission; CA3 Region, Hippocampal; Pyramidal Cells; Humans; Animals
PubMed: 38452088
DOI: 10.1126/science.adg6757 -
Journal of Neurochemistry Apr 2021The synapse is formed between a presynapse (which releases neurotransmitter) and the postsynapse (which transduces this chemical signal). Over the past decade,... (Review)
Review
The synapse is formed between a presynapse (which releases neurotransmitter) and the postsynapse (which transduces this chemical signal). Over the past decade, presynaptic dysfunction has emerged as a key mediator of a series of neurodevelopmental and neurodegenerative disorders. This special issue will highlight some of the important presynaptic molecules and mechanisms that are disrupted in these conditions and reveal potential routes for therapy.
Topics: Animals; Humans; Neurodegenerative Diseases; Neurotransmitter Agents; Presynaptic Terminals; Synapses; Synaptic Vesicles
PubMed: 33728654
DOI: 10.1111/jnc.15319 -
Learning & Memory (Cold Spring Harbor,... May 2024The intricate molecular and structural sequences guiding the formation and consolidation of memories within neuronal circuits remain largely elusive. In this study, we...
The intricate molecular and structural sequences guiding the formation and consolidation of memories within neuronal circuits remain largely elusive. In this study, we investigate the roles of two pivotal presynaptic regulators, the small GTPase Rab3, enriched at synaptic vesicles, and the cell adhesion protein Neurexin-1, in the formation of distinct memory phases within the mushroom body Kenyon cells. Our findings suggest that both proteins play crucial roles in memory-supporting processes within the presynaptic terminal, operating within distinct plasticity modules. These modules likely encompass remodeling and maturation of existing active zones (AZs), as well as the formation of new AZs.
Topics: Animals; Mushroom Bodies; Presynaptic Terminals; Drosophila Proteins; Memory; rab3 GTP-Binding Proteins; Nerve Tissue Proteins; Drosophila; Synaptic Vesicles
PubMed: 38862173
DOI: 10.1101/lm.054013.124