Diving Deep into Synaptic Transmission

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 6708

Special Issue Editors


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Guest Editor
Department of Neurophysiology, Institute for Physiology, University of Würzburg, 97070 Würzburg, Germany
Interests: presynaptic active zones; receptor channels; electrophysiology; super-resolution imaging; high-pressure freezing

E-Mail Website
Guest Editor
1. Department of Neurophysiology, Institute for Physiology, University of Würzburg, 97070 Würzburg, Germany
2. Department of Orthopedic Trauma, Hand, Plastic and Reconstructive Surgery, University Hospital of Würz-burg, 97080 Würzburg, Germany
Interests: active zone; neurotransmission; synaptic plasticity; localization microscopy; traumatic brain injury

Special Issue Information

Dear Colleagues,

Chemical synaptic transmission is currently probed using electrophysiology, pharmacology, (cryogenic) electron and super-resolution light microscopy, and a spectrum of genetically encoded sensors and effectors. Model organisms such as worms, flies and mice are utilized; however, neurons derived from human stem cells have also been increasingly used. Synaptic structure, function and the mechanisms of synaptic differentiation and plasticity during development or aging are central topics. Furthermore, distinct activity states of synapses can be imaged with temporal resolution of milliseconds and at spatial resolution of nanometers. In addition, investigations of disease mechanisms have gained momentum. The aim of this Special Issue is to provide an overview of the most recent advancements in this field by bringing together researchers and publishing their latest studies and discoveries.

Prof. Dr. Manfred Heckmann
Dr. Mila Marie Paul
Guest Editors

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Keywords

  • presynaptic active zone
  • release site
  • synaptic cleft
  • postsynaptic density
  • super-resolution imaging

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Published Papers (5 papers)

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Research

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16 pages, 2961 KiB  
Article
Do Perineuronal Nets Stabilize the Engram of a Synaptic Circuit?
by Varda Lev-Ram, Sakina Palida Lemieux, Thomas J. Deerinck, Eric A. Bushong, Alex J. Perez, Denise R. Pritchard, Brandon H. Toyama, Sung Kyu R. Park, Daniel B. McClatchy, Jeffrey N. Savas, Michael Whitney, Stephen R. Adams, Mark H. Ellisman, John Yates III and Roger Y. Tsien
Cells 2024, 13(19), 1627; https://doi.org/10.3390/cells13191627 - 29 Sep 2024
Cited by 1 | Viewed by 988
Abstract
Perineuronal nets (PNNs), a specialized form of extra cellular matrix (ECM), surround numerous neurons in the CNS and allow synaptic connectivity through holes in its structure. We hypothesize that PNNs serve as gatekeepers that guard and protect synaptic territory and thus may stabilize [...] Read more.
Perineuronal nets (PNNs), a specialized form of extra cellular matrix (ECM), surround numerous neurons in the CNS and allow synaptic connectivity through holes in its structure. We hypothesize that PNNs serve as gatekeepers that guard and protect synaptic territory and thus may stabilize an engram circuit. We present high-resolution and 3D EM images of PNN-engulfed neurons in mice brains, showing that synapses occupy the PNN holes and that invasion of other cellular components is rare. PNN constituents in mice brains are long-lived and can be eroded faster in an enriched environment, while synaptic proteins have a high turnover rate. Preventing PNN erosion by using pharmacological inhibition of PNN-modifying proteases or matrix metalloproteases 9 (MMP9) knockout mice allowed normal fear memory acquisition but diminished long-term memory stabilization, supporting the above hypothesis. Full article
(This article belongs to the Special Issue Diving Deep into Synaptic Transmission)
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10 pages, 1672 KiB  
Article
Enhanced Performance of the Optimized Dye CF583R in Direct Stochastic Optical Reconstruction Microscopy of Active Zones in Drosophila Melanogaster
by Marvin Noß, Dmitrij Ljaschenko and Achmed Mrestani
Cells 2024, 13(17), 1445; https://doi.org/10.3390/cells13171445 - 28 Aug 2024
Viewed by 821
Abstract
Super-resolution single-molecule localization microscopy (SMLM) of presynaptic active zones (AZs) and postsynaptic densities contributed to the observation of protein nanoclusters that are involved in defining functional characteristics and in plasticity of synaptic connections. Among SMLM techniques, direct stochastic optical reconstruction microscopy (d [...] Read more.
Super-resolution single-molecule localization microscopy (SMLM) of presynaptic active zones (AZs) and postsynaptic densities contributed to the observation of protein nanoclusters that are involved in defining functional characteristics and in plasticity of synaptic connections. Among SMLM techniques, direct stochastic optical reconstruction microscopy (dSTORM) depends on organic fluorophores that exert high brightness and reliable photoswitching. While multicolor imaging is highly desirable, the requirements necessary for high-quality dSTORM make it challenging to identify combinations of equally performing, spectrally separated dyes. Red-excited carbocyanine dyes, e.g., Alexa Fluor 647 (AF647) or Cy5, are currently regarded as “gold standard” fluorophores for dSTORM imaging. However, a recent study introduced a set of chemically modified rhodamine dyes, including CF583R, that promise to display similar performance in dSTORM. In this study, we defined CF583R’s performance compared to AF647 and CF568 based on a nanoscopic analysis of Bruchpilot (Brp), a nanotopologically well-characterized scaffold protein at Drosophila melanogaster AZs. We demonstrate equal suitability of AF647, CF568 and CF583R for basal AZ morphometry, while in Brp subcluster analysis CF583R outperforms CF568 and is on par with AF647. Thus, the AF647/CF583R combination will be useful in future dSTORM-based analyses of AZs and other subcellularly located marker molecules and their role in physiological and pathophysiological contexts. Full article
(This article belongs to the Special Issue Diving Deep into Synaptic Transmission)
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18 pages, 3890 KiB  
Article
Conditional Knockout of Neurexins Alters the Contribution of Calcium Channel Subtypes to Presynaptic Ca2+ Influx
by Johannes Brockhaus, Iris Kahl, Mohiuddin Ahmad, Daniele Repetto, Carsten Reissner and Markus Missler
Cells 2024, 13(11), 981; https://doi.org/10.3390/cells13110981 - 5 Jun 2024
Viewed by 1407
Abstract
Presynaptic Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) is a key signal for synaptic vesicle release. Synaptic neurexins can partially determine the strength of transmission by regulating VGCCs. However, it is unknown whether neurexins modulate Ca2+ influx via all VGCC [...] Read more.
Presynaptic Ca2+ influx through voltage-gated Ca2+ channels (VGCCs) is a key signal for synaptic vesicle release. Synaptic neurexins can partially determine the strength of transmission by regulating VGCCs. However, it is unknown whether neurexins modulate Ca2+ influx via all VGCC subtypes similarly. Here, we performed live cell imaging of synaptic boutons from primary hippocampal neurons with a Ca2+ indicator. We used the expression of inactive and active Cre recombinase to compare control to conditional knockout neurons lacking either all or selected neurexin variants. We found that reduced total presynaptic Ca2+ transients caused by the deletion of all neurexins were primarily due to the reduced contribution of P/Q-type VGCCs. The deletion of neurexin1α alone also reduced the total presynaptic Ca2+ influx but increased Ca2+ influx via N-type VGCCs. Moreover, we tested whether the decrease in Ca2+ influx induced by activation of cannabinoid receptor 1 (CB1-receptor) is modulated by neurexins. Unlike earlier observations emphasizing a role for β-neurexins, we found that the decrease in presynaptic Ca2+ transients induced by CB1-receptor activation depended more strongly on the presence of α-neurexins in hippocampal neurons. Together, our results suggest that neurexins have unique roles in the modulation of presynaptic Ca2+ influx through VGCC subtypes and that different neurexin variants may affect specific VGCCs. Full article
(This article belongs to the Special Issue Diving Deep into Synaptic Transmission)
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13 pages, 2645 KiB  
Article
Versatile Endogenous Editing of GluRIIA in Drosophila melanogaster
by Constantin J. Beckers, Achmed Mrestani, Fabian Komma and Sven Dannhäuser
Cells 2024, 13(4), 323; https://doi.org/10.3390/cells13040323 - 10 Feb 2024
Cited by 1 | Viewed by 1811
Abstract
Glutamate receptors at the postsynaptic side translate neurotransmitter release from presynapses into postsynaptic excitation. They play a role in many forms of synaptic plasticity, e.g., homeostatic scaling of the receptor field, activity-dependent synaptic plasticity and the induction of presynaptic homeostatic potentiation (PHP). The [...] Read more.
Glutamate receptors at the postsynaptic side translate neurotransmitter release from presynapses into postsynaptic excitation. They play a role in many forms of synaptic plasticity, e.g., homeostatic scaling of the receptor field, activity-dependent synaptic plasticity and the induction of presynaptic homeostatic potentiation (PHP). The latter process has been extensively studied at Drosophila melanogaster neuromuscular junctions (NMJs). The genetic removal of the glutamate receptor subunit IIA (GluRIIA) leads to an induction of PHP at the synapse. So far, mostly imprecise knockouts of the GluRIIA gene have been utilized. Furthermore, mutated and tagged versions of GluRIIA have been examined in the past, but most of these constructs were not expressed under endogenous regulatory control or involved the mentioned imprecise GluRIIA knockouts. We performed CRISPR/Cas9-assisted gene editing at the endogenous locus of GluRIIA. This enabled the investigation of the endogenous expression pattern of GluRIIA using tagged constructs with an EGFP and an ALFA tag for super-resolution immunofluorescence imaging, including structured illumination microscopy (SIM) and direct stochastic optical reconstruction microscopy (dSTORM). All GluRIIA constructs exhibited full functionality and PHP could be induced by philanthotoxin at control levels. By applying hierarchical clustering algorithms to analyze the dSTORM data, we detected postsynaptic receptor cluster areas of ~0.15 µm2. Consequently, our constructs are suitable for ultrastructural analyses of GluRIIA. Full article
(This article belongs to the Special Issue Diving Deep into Synaptic Transmission)
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Review

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21 pages, 1130 KiB  
Review
Age-Related Homeostatic Plasticity at Rodent Neuromuscular Junctions
by Yizhi Li, Yomna Badawi and Stephen D. Meriney
Cells 2024, 13(20), 1684; https://doi.org/10.3390/cells13201684 - 11 Oct 2024
Viewed by 745
Abstract
Motor ability decline remains a major threat to the quality of life of the elderly. Although the later stages of aging co-exist with degenerative pathologies, the long process of aging is more complicated than a simple and gradual degeneration. To combat senescence and [...] Read more.
Motor ability decline remains a major threat to the quality of life of the elderly. Although the later stages of aging co-exist with degenerative pathologies, the long process of aging is more complicated than a simple and gradual degeneration. To combat senescence and the associated late-stage degeneration of the neuromuscular system, it is imperative to examine changes that occur during the long process of aging. Prior to late-stage degeneration, age-induced changes in the neuromuscular system trigger homeostatic plasticity. This unique phenomenon may be important for the maintenance of the neuromuscular system during the early stages of aging. In this review, we will focus on age-induced changes in neurotransmission at the neuromuscular junction, providing the potential mechanisms responsible for these changes. The goal is to highlight these key elements and their role in regulating neurotransmission, facilitating future research efforts to combat late-stage degeneration in the neuromuscular system by preserving the functional and structural integrity of these elements prior to the late stage of aging. Full article
(This article belongs to the Special Issue Diving Deep into Synaptic Transmission)
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