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New Insights into Synapse Structure and Function

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (10 March 2024) | Viewed by 10408

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Special Issue Editor

Prof. Dr. Sumiko Mochida

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Guest Editor

Department of Physiology, Tokyo Medical University, 1-1 Shinjuku-6-chome, Shinju-ku, Tokyo 160-8402, Japan
Interests: synaptic transmission; presynaptic terminals; neurotransmitter release; presynaptic calcium channels; presynaptic proteins; calcium-binding proteins

Special Issue Information

Dear Colleagues,

Synapse is a key structure for signal transmission in neuronal networks. The synaptic function is controlled by multiple processes related to protein-protein reactions in both presynaptic terminals and postsynaptic neurons. Neuronal activity regulates synaptic strength and induces synaptic plasticity. The synaptic plasticity is important feature for neuronal networks not only in formation of memory and learning but also in flexible basic synaptic transmission. Over the last decade, improvements in research techniques enable us to gather insights from different approaches into synaptic structure and function, which have promoted important developments in research in synaptic transmission. This Special Issue is seeking facilitate new findings to address key aspects of the synaptic structure and function, including synapse formation, development and aging. This Special Issue will be dedicated to the structure and function of synapse, welcoming all those studies that will help to clarify it.

Prof. Dr. Sumiko Mochida
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

synaptic structure
synaptic transmission
synaptic function
synaptic plasticity
neurotransmitter release
neutotransmitter receptor

Published Papers (6 papers)

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Research

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12 pages, 3694 KiB

Open AccessArticle

The Relative Contribution of Glycine–GABA Cotransmission in the Core of the Respiratory Network

by Ali Harb, Charlotte Tacke, Behnam Vafadari and Swen Hülsmann

Int. J. Mol. Sci. 2024, 25(6), 3128; https://doi.org/10.3390/ijms25063128 - 8 Mar 2024

Viewed by 596

Abstract

The preBötzinger complex (preBötC) and the Bötzinger complex (BötC) are interconnected neural circuits that are involved in the regulation of breathing in mammals. Fast inhibitory neurotransmission is known to play an important role in the interaction of these two regions. Moreover, the corelease of glycine and GABA has been described in the respiratory network, but the contribution of the individual neurotransmitter in different pathways remains elusive. In sagittal brainstem slices of neonatal mice, we employed a laser point illumination system to activate glycinergic neurons expressing channelrhodopsin-2 (ChR2). This approach allowed us to discern the contribution of glycine and GABA to postsynaptic currents of individual whole-cell clamped neurons in the preBötC and BötC through the application of glycine and GABA receptor-specific antagonists. In more than 90% of the recordings, both transmitters contributed to the evoked IPSCs, with the glycinergic component being larger than the GABAergic component. The GABAergic component appeared to be most prominent when stimulation and recording were both performed within the preBötC. Taken together, our data suggest that GABA–glycine cotransmission is the default mode in the respiratory network of neonatal mice with regional differences that may be important in tuning the network activity. Full article

(This article belongs to the Special Issue New Insights into Synapse Structure and Function)

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15 pages, 3098 KiB

Open AccessArticle

Δ⁸-THC Induces Up-Regulation of Glutamatergic Pathway Genes in Differentiated SH-SY5Y: A Transcriptomic Study

by Ivan Anchesi, Giovanni Schepici, Luigi Chiricosta, Agnese Gugliandolo, Stefano Salamone, Diego Caprioglio, Federica Pollastro and Emanuela Mazzon

Int. J. Mol. Sci. 2023, 24(11), 9486; https://doi.org/10.3390/ijms24119486 - 30 May 2023

Cited by 2 | Viewed by 1153

Abstract

Cannabinoids, natural or synthetic, have antidepressant, anxiolytic, anticonvulsant, and anti-psychotic properties. Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (Δ⁹-THC) are the most studied cannabinoids, but recently, attention has turned towards minor cannabinoids. Delta-8-tetrahydrocannabinol (Δ⁸-THC), an isomer of Δ⁹-THC, is a compound for which, to date, there is no evidence of its role in the modulation of synaptic pathways. The aim of our work was to evaluate the effects of Δ⁸-THC on differentiated SH-SY5Y human neuroblastoma cells. Using next generation sequencing (NGS), we investigated whether Δ⁸-THC could modify the transcriptomic profile of genes involved in synapse functions. Our results showed that Δ⁸-THC upregulates the expression of genes involved in the glutamatergic pathway and inhibits gene expression at cholinergic synapses. Conversely, Δ⁸-THC did not modify the transcriptomic profile of genes involved in the GABAergic and dopaminergic pathways. Full article

(This article belongs to the Special Issue New Insights into Synapse Structure and Function)

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19 pages, 12733 KiB

Open AccessArticle

A Postsynaptic Density Immediate Early Gene-Based Connectome Analysis of Acute NMDAR Blockade and Reversal Effect of Antipsychotic Administration

by Annarita Barone, Giuseppe De Simone, Mariateresa Ciccarelli, Elisabetta Filomena Buonaguro, Carmine Tomasetti, Anna Eramo, Licia Vellucci and Andrea de Bartolomeis

Int. J. Mol. Sci. 2023, 24(5), 4372; https://doi.org/10.3390/ijms24054372 - 22 Feb 2023

Cited by 2 | Viewed by 1813

Abstract

Although antipsychotics’ mechanisms of action have been thoroughly investigated, they have not been fully elucidated at the network level. We tested the hypothesis that acute pre-treatment with ketamine (KET) and administration of asenapine (ASE) would modulate the functional connectivity of brain areas relevant to the pathophysiology of schizophrenia, based on transcript levels of Homer1a, an immediate early gene encoding a key molecule of the dendritic spine. Sprague–Dawley rats (n = 20) were assigned to KET (30 mg/kg) or vehicle (VEH). Each pre-treatment group (n = 10) was randomly split into two arms, receiving ASE (0.3 mg/kg), or VEH. Homer1a mRNA levels were evaluated by in situ hybridization in 33 regions of interest (ROIs). We computed all possible pairwise Pearson correlations and generated a network for each treatment group. Acute KET challenge was associated with negative correlations between the medial portion of cingulate cortex/indusium griseum and other ROIs, not detectable in other treatment groups. KET/ASE group showed significantly higher inter-correlations between medial cingulate cortex/indusium griseum and lateral putamen, the upper lip of the primary somatosensory cortex, septal area nuclei, and claustrum, in comparison to the KET/VEH network. ASE exposure was associated with changes in subcortical-cortical connectivity and an increase in centrality measures of the cingulate cortex and lateral septal nuclei. In conclusion, ASE was found to finely regulate brain connectivity by modelling the synaptic architecture and restoring a functional pattern of interregional co-activation. Full article

(This article belongs to the Special Issue New Insights into Synapse Structure and Function)

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12 pages, 1814 KiB

Open AccessArticle

Daily Brief Heat Therapy Reduces Seizures in A350V IQSEC2 Mice and Is Associated with Correction of AMPA Receptor-Mediated Synaptic Dysfunction

by Reem Jada, Veronika Borisov, Eliezer Laury, Shmuel Halpert, Nina S. Levy, Shlomo Wagner, Shai Netser, Randall Walikonis, Ido Carmi, Shai Berlin and Andrew P. Levy

Int. J. Mol. Sci. 2023, 24(4), 3924; https://doi.org/10.3390/ijms24043924 - 15 Feb 2023

Cited by 2 | Viewed by 1814

Abstract

Purposeful induction of fever for healing, including the treatment of epilepsy, was used over 2000 years ago by Hippocrates. More recently, fever has been demonstrated to rescue behavioral abnormalities in children with autism. However, the mechanism of fever benefit has remained elusive due in large part to the lack of appropriate human disease models recapitulating the fever effect. Pathological mutations in the IQSEC2 gene are frequently seen in children presenting with intellectual disability, autism and epilepsy. We recently described a murine A350V IQSEC2 disease model, which recapitulates important aspects of the human A350V IQSEC2 disease phenotype and the favorable response to a prolonged and sustained rise in body core temperature in a child with the mutation. Our goal has been to use this system to understand the mechanism of fever benefit and then develop drugs that can mimic this effect and reduce IQSEC2-associated morbidity. In this study, we first demonstrate a reduction in seizures in the mouse model following brief periods of heat therapy, similar to what was observed in a child with the mutation. We then show that brief heat therapy is associated with the correction of synaptic dysfunction in neuronal cultures of A350V mice, likely mediated by Arf6-GTP. Full article

(This article belongs to the Special Issue New Insights into Synapse Structure and Function)

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Review

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16 pages, 917 KiB

Open AccessReview

Role of Neuronal TRPC6 Channels in Synapse Development, Memory Formation and Animal Behavior

by Nikita Zernov and Elena Popugaeva

Int. J. Mol. Sci. 2023, 24(20), 15415; https://doi.org/10.3390/ijms242015415 - 21 Oct 2023

Cited by 2 | Viewed by 1235

Abstract

The transient receptor potential cation channel, subfamily C, member 6 (TRPC6), has been believed to adjust the formation of an excitatory synapse. The positive regulation of TRPC6 engenders synapse enlargement and improved learning and memory in animal models. TRPC6 is involved in different synaptoprotective signaling pathways, including antagonism of N-methyl-D-aspartate receptor (NMDAR), activation of brain-derived neurotrophic factor (BDNF) and postsynaptic store-operated calcium entry. Positive regulation of TRPC6 channels has been repeatedly shown to be good for memory formation and storage. TRPC6 is mainly expressed in the hippocampus, particularly in the dentate granule cells, cornu Ammonis 3 (CA3) pyramidal cells and gamma-aminobutyric acid (GABA)ergic interneurons. It has been observed that TRPC6 agonists have a great influence on animal behavior including memory formation and storage The purpose of this review is to collect the available information on the role of TRPC6 in memory formation in various parts of the brain to understand how TRPC6-specific pharmaceutical agents will affect memory in distinct parts of the central nervous system (CNS). Full article

(This article belongs to the Special Issue New Insights into Synapse Structure and Function)

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21 pages, 1607 KiB

Open AccessReview

Advances in the Electrophysiological Recordings of Long-Term Potentiation

by Feixu Jiang, Stephen Temitayo Bello, Qianqian Gao, Yuanying Lai, Xiao Li and Ling He

Int. J. Mol. Sci. 2023, 24(8), 7134; https://doi.org/10.3390/ijms24087134 - 12 Apr 2023

Cited by 3 | Viewed by 3067

Abstract

Understanding neuronal firing patterns and long-term potentiation (LTP) induction in studying learning, memory, and neurological diseases is critical. However, recently, despite the rapid advancement in neuroscience, we are still constrained by the experimental design, detection tools for exploring the mechanisms and pathways involved in LTP induction, and detection ability of neuronal action potentiation signals. This review will reiterate LTP-related electrophysiological recordings in the mammalian brain for nearly 50 years and explain how excitatory and inhibitory neural LTP results have been detected and described by field- and single-cell potentials, respectively. Furthermore, we focus on describing the classic model of LTP of inhibition and discuss the inhibitory neuron activity when excitatory neurons are activated to induce LTP. Finally, we propose recording excitatory and inhibitory neurons under the same experimental conditions by combining various electrophysiological technologies and novel design suggestions for future research. We discussed different types of synaptic plasticity, and the potential of astrocytes to induce LTP also deserves to be explored in the future. Full article

(This article belongs to the Special Issue New Insights into Synapse Structure and Function)

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