Article
Cell Biology
Daniele Ferrante, Bruno Sterlini, Cosimo Prestigio, Antonella Marte, Anna Corradi, Franco Onofri, Giorgio Tortarolo, Giuseppe Vicidomini, Andrea Petretto, Jessica Muia, Agnes Thalhammer, Pierluigi Valente, Lorenzo A. Cingolani, Fabio Benfenati, Pietro Baldelli
Summary: Loss-of-function mutations in PRRT2 lead to paroxysmal disorders by affecting the Ca2+ dependence of glutamatergic transmission. The decrease in excitatory postsynaptic currents induced by PRRT2 deletion is related to a reduced contribution of P/Q-type Ca2+ channels. PRRT2 interacts directly with P/Q-type Ca2+ channels to ensure the physiological Ca2+ sensitivity of release machinery at glutamatergic synapses.
Review
Biochemistry & Molecular Biology
Sumiko Mochida
Summary: Action potentials trigger neurotransmitter release and control replenishment of release sites with synaptic vesicles. Recent studies have revealed millisecond-scale dynamics of synaptic vesicles. Proteins regulate replenishment by sensing Ca2+ influx.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Nadja T. Hofer, Alexandra Pinggera, Yuliia V. Nikonishyna, Petronel Tuluc, Eva M. Fritz, Gerald J. Obermair, Joerg Striessnig
Summary: Low voltage-activated Cav1.3 L-type Ca2+ channels with alternative splicing in the C-terminus have functional implications in neuronal excitability and learning. Inclusion of exons 8b, 11, and 32 in Cav1.3(S) shifts activation and inactivation to more negative voltages. Exons 11 and 32 contribute significantly to native channels in the brain, influencing both wild-type and mutant Cav1.3 channel properties.
Article
Cell Biology
Baris Alten, Natalie J. Guzikowski, Zack Zurawski, Heidi E. Hamm, Ege T. Kavalali
Summary: Inhibition of neurotransmitter release plays a fundamental role in neuromodulation, but the mechanisms underlying inhibition of spontaneous release are still unclear. This study investigates the inhibition of spontaneous glutamate and GABA release by GABA(B) receptors and reveals that the inhibition relies on G beta gamma subunit action at the membrane, with different mechanisms for glutamate and GABA release.
Article
Multidisciplinary Sciences
Pei-Yi Lin, Lulu Y. Chen, Peng Zhou, Sung-Jin Lee, Justin H. Trotter, Thomas C. Suedhof
Summary: Recent research has shown that the deletion of Nrxn2 unexpectedly leads to an increase in excitatory synapse numbers and their presynaptic release probability, suggesting a role of Nrxn2 in restricting synapse assembly. Cultured hippocampal neurons have been used to study the synaptic function and mechanism of Nrxn2, revealing that certain splice variants of Nrxn2 restrict synapse numbers and restrain their release probability. These findings are significant for understanding the mechanism of synapse assembly.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Tzu-Kang Lin, Chi-Feng Hung, Jing-Ru Weng, Ting-Yang Hsieh, Su-Jane Wang
Summary: This study found that Kaempferol 3-rhamnoside (KR) can inhibit 4-aminopyridine (4-AP)-evoked glutamate release. The inhibitory effect of KR is linked to the omission of external Ca2+ or the depletion of glutamate in synaptic vesicles, as well as the suppression of P/Q-type Ca2+ channel activity. Additionally, KR reduces the increase in Ca2+ concentration and the phosphorylation of CaMKII and its substrate synapsin I.
Article
Biochemistry & Molecular Biology
Suk-Young Song, Soonil Pyo, Sungchul Choi, Hee Sang Oh, Jung Hwa Seo, Ji Hea Yu, Ahreum Baek, Yoon-Kyum Shin, Hoo Young Lee, Ja Young Choi, Sung-Rae Cho
Summary: Environmental enrichment (EE) has a significant therapeutic effect on HIE, upregulating the expression of the Ca-v 2.1 channel and presynaptic proteins, leading to improvements in motor and cognitive performance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
F. Locatelli, T. Soda, I Montagna, S. Tritto, L. Botta, F. Prestori, E. D'Angelo
Summary: Research has found that excitatory synapses on Golgi cells in the cerebellum exhibit a unique voltage dependence in long-term plasticity, with activation of T-type and L-type Ca2+ channels playing important roles in inducing LTP and LTD. Additionally, there is an inverted relationship between plasticity at mossy fiber-Golgi cell synapses and mossy fiber-granule cell synapses in terms of voltage dependence.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Natali L. Chanaday, Elena Nosyreva, Ok-Ho Shin, Hua Zhang, Iltan Aklan, Deniz Atasoy, Ilya Bezprozvanny, Ege T. Kavalali
Summary: The study found that acute ER Ca2+ depletion increases presynaptic Ca2+ levels and glutamate release, while chronic ER stress leads to syt7-dependent potentiation of spontaneous glutamate release. Inhibition of SOCE or syt7-driven fusion during ER stress can partially restore basal neurotransmission.
Article
Genetics & Heredity
Anjan Hazra, Amita Pal, Anirban Kundu
Summary: This study used a transcriptome-based approach to identify 54,526 AS events in Vigna mungo, involving 15,506 AS genes and resulting in 57,405 transcript isoforms. The results revealed the regulatory role of AS in diverse functions and showed that splice variants of transcription factors are expressed differently across tissues and environmental cues. The study suggests that AS plays a crucial role in regulating gene expression in different tissues and stressful conditions.
FUNCTIONAL & INTEGRATIVE GENOMICS
(2023)
Article
Biochemistry & Molecular Biology
Anna Chang, Chi-Feng Hung, Pei-Wen Hsieh, Horng-Huey Ko, Su-Jane Wang
Summary: Eupafolin exerts its neuroprotective effects by inhibiting glutamate release, reducing intracellular calcium levels, and disrupting the CaMKII/synapsin I pathway.
BIOMOLECULES & THERAPEUTICS
(2021)
Article
Cardiac & Cardiovascular Systems
Pablo Montanes-Agudo, Simona Aufiero, Eva N. Schepers, Ingeborg van der Made, Lucia Cocera-Ortega, Auriane C. Ernault, Stephane Richard, Diederik W. D. Kuster, Vincent M. Christoffels, Yigal M. Pinto, Esther E. Creemers
Summary: This study aims to investigate the function and relevance of QKI in the adult mouse heart. The results show that QKI regulates the alternative splicing of multiple genes and affects the functional properties of cardiomyocytes. Loss of QKI leads to severe disruption of sarcomeres and rapid development of heart failure.
CARDIOVASCULAR RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Dariia O. Dryn, Mariia I. Melnyk, Donal Melanaphy, Igor V. Kizub, Christopher D. Johnson, Alexander V. Zholos
Summary: This study demonstrates for the first time the biphasic contractile reaction of TRPV4 in rat pulmonary artery, showing relaxation followed by a contraction. The relaxation phase is induced by BKCa activation, while the subsequent contraction is mediated by TRPV4-dependent depolarization and Ca-L activation. Similar changes in membrane potential are observed with the activation of TRPM8 in the rat tail artery.
Article
Neurosciences
Marijn Kuijpers, Gaga Kochlamazashvili, Alexander Stumpf, Dmytro Puchkov, Aarti Swaminathan, Max Thomas Lucht, Eberhard Krause, Tanja Maritzen, Dietmar Schmitz, Volker Haucke
Summary: This study demonstrates that loss of neuronal autophagy leads to selective accumulation of tubular endoplasmic reticulum (ER) in axons, resulting in increased excitatory neurotransmission and compromised postnatal viability in vivo. The elevated excitatory neurotransmission is caused by increased calcium release from ER stores via ryanodine receptors accumulated in axons and at presynaptic sites. Neuronal autophagy controls axonal ER calcium stores to regulate neurotransmission in healthy neurons and in the brain.
Article
Mathematics, Applied
Suriyakamol Thongjob, Kamsing Nonlaopon, Sortiris K. Ntouyas
Summary: This paper examines (p, q)-Hardy type inequalities, Holder integral inequality, and Minkowski integral inequality for (p, q)-integrable functions, with the results reducing to classical results under certain conditions.
Article
Cell Biology
Rudi Tong, Thomas Edward Chater, Nigel John Emptage, Yukiko Goda
Summary: Dendrites play a crucial role in integrating incoming synaptic information, with individual dendritic branches considered as signal processing units. This study explores how neighboring synapses shape the boundaries of functional dendritic units, highlighting the involvement of multiple signaling pathways in regulating the local pattern of synaptic strengths.
Article
Neurosciences
Thomas E. Chater, Yukiko Goda
Summary: Synaptic strength changes based on activity, with inactive neighbouring synapses also potentially changing. These heterosynaptic changes occur in various brain circuits across species, but their molecular mechanisms remain unclear. They can mirror or oppose homosynaptic plasticity, providing useful functionality to the circuit. Unanswered questions remain, but the future of understanding synaptic plasticity looks promising.
CURRENT OPINION IN NEUROBIOLOGY
(2021)
Article
Biology
Waja Wegner, Heinz Steffens, Carola Gregor, Fred Wolf, Katrin Willig, Yukiko Goda
Summary: This study investigated the effects of environmental enrichment on the morphology and dynamics of individual synapses. The results showed that environmental enrichment can enhance the uniformity of synaptic strength and lead to a more dynamic topography of the PSD95 nanoorganization.
Review
Biochemistry & Molecular Biology
Margaux Saint-Martin, Yukiko Goda
Summary: Astrocytes play a crucial role in regulating brain functions, not only through supporting neuronal activity but also by directly influencing information processing and behavior through their interactions with synapses. The involvement of astrocytic cell adhesion proteins in synapse formation and function highlights the importance of reevaluating the traditional neurocentric view.
Review
Neurosciences
Thomas Edward Chater, Yukiko Goda
Summary: The translation discusses the dependence of neurotransmission on the number, position, and composition of receptor proteins on the postsynaptic neuron. It specifically focuses on the role and regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) in synaptic activity.
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Philipe R. F. Mendonca, Erica Tagliatti, Helen Langley, Dimitrios Kotzadimitriou, Criseida G. Zamora-Chimal, Yulia Timofeeva, Kirill E. Volynski
Summary: This study reveals the variation in synchronous and asynchronous release ratio among synaptic outputs from single pyramidal cells, and demonstrates that low release probability synapses have reduced synchronicity. Additionally, the distribution of asynchronous release sites is more widespread within the release area.
NATURE COMMUNICATIONS
(2022)
Review
Neurosciences
Kelvin K. Hui, Thomas E. Chater, Yukiko Goda, Motomasa Tanaka
Summary: Excitatory-inhibitory (E-I) imbalance is a contributing factor to various neurodevelopmental disorders. Dysregulation of GABA neurotransmission and chloride homeostasis is associated with these abnormalities. Recent evidence suggests that the GABA-shift phenomenon may be involved in neuropsychiatric disorders. This review discusses the cell signaling and regulatory mechanisms underlying the GABA-shift, explores the interactions between GABAergic interneurons and other cell types, and outlines recent progress in targeting NKCC1 and KCC2 as a therapeutic strategy.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Agnes Thalhammer, Mario Fontanini, Jiuyun Shi, Denis Scaini, Luca Recupero, Alexander Evtushenko, Ying Fu, Suraj Pavagada, Andrea Bistrovic-Popov, Ljiljana Fruk, Bozhi Tian, Laura Ballerini
Summary: Nano-enabled neural interfaces can optically modulate single neurons and affect sensory circuit processing. Moreover, functionalized nano-photodiodes allow for light activation of specific synaptic pathways. This approach provides a new perspective in studying the relationship between neural activity and behavioral outcomes with low invasiveness.
Article
Medicine, Research & Experimental
Fanny Jaudon, Agnes Thalhammer, Lorena Zentilin, Lorenzo A. Cingolani
Summary: Research shows that haplo-insufficiency of the Itgb3 gene affects cortical network excitability by promoting extra-synaptic signaling of the mGluR5 receptor. Using CRISPR activation, the neuronal Itgb3 haplo-insufficiency can be corrected, effectively restoring network excitability.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biology
Edoardo Moretto, Federico Miozzo, Anna Longatti, Caroline Bonnet, Francoise Coussen, Fanny Jaudon, Lorenzo A. Cingolani, Maria Passafaro
Summary: In rat hippocampal neurons, the tetraspanin TSPAN5 was found to promote exocytosis of AMPA receptors without affecting their internalisation. This function is mediated by TSPAN5 interacting with the adaptor protein complex AP4 and Stargazin, possibly using recycling endosomes as a delivery route. This study highlights the importance of TSPAN5 as a new adaptor protein regulating AMPA receptor trafficking.
Article
Biochemistry & Molecular Biology
Lorenzo A. Cingolani, Agnes Thalhammer, Fanny Jaudon, Jessica Muia, Gabriele Baj
Summary: Using superresolution structured illumination microscopy, we investigated the nanoscale organization of two Ca(V)2.1 splice isoforms at presynaptic terminals. We found that Ca(V)2.1[EFa] is more tightly co-localized with presynaptic markers, indicating that alternative splicing plays a crucial role in the synaptic organization of Ca(V)2.1 channels.
BIOLOGICAL CHEMISTRY
(2023)
Article
Biology
Christopher A. Norman, Shyam S. Krishnakumar, Yulia Timofeeva, Kirill E. Volynski
Summary: This study uses a computational modelling framework to quantitatively assess how the molecular architecture of the fusion clamp affects synaptic vesicle exocytosis. The results support the "release-of-inhibition" model of fast calcium-activated synaptic vesicle fusion and show that dual binding of synaptotagmin-1 and synaptotagmin-7 to the same SNARE complex enables synergistic regulation of neurotransmitter release kinetics and plasticity. The developed framework provides a powerful tool to test molecular models of calcium-triggered neurotransmitter release in silico.
COMMUNICATIONS BIOLOGY
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
Yukiko Goda, Peter Chipman, Chi Chung Alan Fung, Alejandra Pazo Fernandez, Abhilash Sawant, Angelo Tedoldi, Atsushi Kawai, Sunita Ghimire Gautam, Mizuki Kurosawa, Manabu Abe, Kenji Sakimura, Tomoki Fukai
JOURNAL OF NEUROCHEMISTRY
(2022)