Article
Multidisciplinary Sciences
Ryota Fukaya, Marta Maglione, Stephan J. Sigrist, Takeshi Sakaba
Summary: This study suggests a potential mechanism for the cAMP-dependent increase in neurotransmission at hippocampal mossy fiber-CA3 synapses, involving an accumulation of active zone Ca2+ channels. Experimental results indicate an increase in the local Ca2+ concentration at the release site following potentiation, driven by rapid Ca2+ channel accumulation, rather than changes in intracellular Ca2+ sensitivity. Various microscopy techniques provide insights into the underlying mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Neurosciences
Jithin D. Nair, Kevin A. Wilkinson, Jeremy M. Henley, Jack R. Mellor
Summary: This article reviews the roles of kainate receptors in synaptic plasticity, focusing on their impact on postsynaptic signaling and presynaptic auto-receptor functions. It also explores the plasticity of kainate receptors themselves and their contribution to synaptic transmission plasticity.
Article
Neurosciences
Carla C. Schmidt, Fang Zheng, Christian Alzheimer
Summary: Activin, a member of the TGF-beta family, has been found to have a neuromodulatory effect on mossy cells (MCs), affecting their excitatory and inhibitory inputs. Increased activin can enhance MC activity, while disruption of activin receptor signaling can reduce MC firing.
Article
Neurosciences
Yixing Du, Faith H. Brennan, Phillip G. Popovich, Min Zhou
Summary: This study investigates the role of microglia in regulating the structure and function of astrocytes in the mouse hippocampus, revealing that depletion of microglia disrupts astrocyte syncytial isopotentiality and dye coupling, leading to reduced synaptic transmission in neurons. Activation of microglia enhances synaptic transmission, while leaving astrocyte network function unaffected.
Review
Neurosciences
Carolyn Twible, Rober Abdo, Qi Zhang
Summary: The article discusses the impact of epilepsy on approximately 50 million people worldwide, with 60% of adult epilepsies having a focal onset. It delves into the role of astrocytes in temporal lobe epilepsy (TLE), particularly focusing on histopathological diagnosis, mossy fiber sprouting, and the potential contribution of astrocytes to cellular alterations in TLE patients. The review highlights proposed signaling pathways, cellular mechanisms, histological observations, and clinical correlations in human patients.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Bing-Xue Li, Hua Jin, Guang-Jian Zhang, Li-Na Cui, Chun-Ping Chu, De-Lai Qiu
Summary: The study demonstrated that noradrenaline depresses mossy fiber-granule cell synaptic transmission evoked by facial stimulation through the alpha-2 adrenergic receptor in the cerebellum of mice.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Neurosciences
Fumeng Zheng, Haruyuki Kamiya
Summary: Modification of axonal excitability affects information transfer in the brain, but the functional significance of this modulation remains unclear. This study focused on the activity-dependent broadening of action potentials in the hippocampal mossy fibers and found that it is dependent on the inactivation of axonal K+ channels. Computer simulations showed that removing the inactivation process abolished the use-dependent broadening of action potentials. This highlights the critical role of K+ channel inactivation in regulating axonal excitability and short-term plasticity at this synapse.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Kyoung Hoon Jeong, Jing Zhu, Soojin Park, Won-Joo Kim
Summary: The role of TRPV6 in epilepsy is unclear. This study found that TRPV6 expression is upregulated in the hippocampus of a pilocarpine-induced status epilepticus model and is related to abnormal MF sprouting (MFS) and the incidence of seizures. In vitro experiments showed that TRPV6 expression can regulate axonal formation in cultured hippocampal neurons. Furthermore, TRPV6 is involved in the regulation of Akt-glycogen synthase kinase-3-beta activity, which is related to axonal outgrowth. Therefore, TRPV6 may regulate the formation of aberrant synaptic circuits during epileptogenesis.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Felipe Antonio Mendez-Salcido, Mayra Itzel Torres-Flores, Benito Ordaz, Fernando Pena-Ortega
Summary: Neuron-microglia communication through the Cx3cr1-Cx3cl1 axis is essential for neural circuit development and function. Cx3cr1-deficient mice show changes in microglial and synaptic terminals morphology and density, leading to alterations in daily activities and spatial navigation. These cognitive deficiencies are associated with synaptic dysfunction in the CA3 region of the hippocampus and weakened functional connectivity among CA3 neurons in Cx3cr1-deficient mice. These alterations may arise early in postnatal development, a critical period for microglia-dependent neural circuit refinement.
Article
Neurosciences
Eleonore Hardy, Martine Cohen-Salmon, Nathalie Rouach, Armelle Rancillac
Summary: The study found that astrocytes, through connexin 30 (Cx30), differentially alter the electrophysiological and morphological properties of hippocampal cells, modulating both excitatory and inhibitory inputs.
Article
Neurosciences
Benjamin Owen, Edyta Bichler, Morris Benveniste
Summary: This study investigates changes in synaptic transmission with progression of chronic epilepsy, finding that rats treated with pilocarpine show alterations in synaptic characteristics at different time points, possibly related to depletion of neurotransmitter vesicles.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Multidisciplinary Sciences
Jithin D. Nair, Kevin A. Wilkinson, Busra P. Yucel, Christophe Mulle, Bryce Vissel, Jack Mellor, Jeremy M. Henley
Summary: Editing of GluK2 Q/R influences the synaptic expression and plasticity of AMPARs by modulating the ionotropic/metabotropic balance of KAR signaling.
Article
Neurosciences
Kyle A. Brown, Panos Zanos, Chris F. Powels, Connor J. Fix, Michael Michaelides, Edna F. R. Pereira, Ruin Moaddel, Todd D. Gould
Summary: Benzethonium chloride (BZT) is an excipient commonly used in ketamine drug formulations, and recent research suggests that BZT has pharmacological activity. This study investigated the affinity of BZT for neurotransmitter receptors and transporters, its effects on synaptic transmission, and its distribution in the body. The results showed that BZT binds to various receptors and transporters, enhances synaptic potentials in the hippocampus, and can be detected in the plasma but not in the brain after administration. These findings suggest that previous studies attributing pharmacological effects to ketamine may be influenced by BZT and warrant further investigation of BZT's functional impact.
Article
Biochemistry & Molecular Biology
Ildiko Piszar, Magor L. Lorincz
Summary: Serotonin plays an important role in regulating sensory inputs in the olfactory cortex by modulating synaptic transmission.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Developmental Biology
Yurika Nakanishi, Satoshi Akinaga, Koki Osawa, Natusmi Suzuki, Ayaka Sugeno, Papachan Kolattukudy, Yoshio Goshima, Toshio Ohshima
Summary: This study revealed that CRMP4 is involved in the pruning of the infrapyramidal bundle (IPB) in the hippocampus, while CRMP1 is not. Additionally, CRMP2 was found to mediate IPB pruning through Nrp2.
DEVELOPMENTAL NEUROBIOLOGY
(2022)
Article
Clinical Neurology
Karen Suetterlin, Emma Matthews, Richa Sud, Samuel McCall, Doreen Fialho, James Burge, Dipa Jayaseelan, Andrea Haworth, Mary G. Sweeney, Dimitri M. Kullmann, Stephanie Schorge, Michael G. Hanna, Roope Mannikko
Summary: High-throughput DNA sequencing is widely used in the diagnosis of neurological and neuromuscular disorders. However, interpreting the clinical significance and inheritance pattern of variants remains challenging. This study focuses on the evaluation of variants in the ClC-1 channel, which is central to the diagnosis of myotonia congenita. The results show that functional characterization of variants improves the interpretation of their pathogenicity and inheritance pattern.
Article
Neurosciences
Olga Tyurikova, Pei-Yu Shih, Yulia Dembitskaya, Leonid P. Savtchenko, Thomas J. McHugh, Dmitri A. Rusakov, Alexey Semyanov
Summary: Glutamatergic transmission through postsynaptic NMDA receptors induces K+ efflux, which enhances glutamate release in astrocytes and reduces glutamate uptake, forming a feedback loop.
Editorial Material
Psychology, Multidisciplinary
Maria Jose Alvarez-Alonso, Ricardo Scott, Isabel Morales-Munoz
FRONTIERS IN PSYCHOLOGY
(2022)
Article
Clinical Neurology
Vincenzo Salpietro, Valentina Galassi Deforie, Stephanie Efthymiou, Emer O'Connor, Anna Marce-Grau, Reza Maroofian, Pasquale Striano, Federico Zara, Michelle M. Morrow, Adi Reich, Amy Blevins, Julia Sala-Coromina, Andrea Accogli, Sara Fortuna, Marie Alesandrini, P. Y. Billie Au, Nilika Shah Singhal, Benjamin Cogne, Bertrand Isidor, Michael G. Hanna, Alfons Macaya, Dimitri M. Kullmann, Henry Houlden, Roope Mannikko
Summary: Novel mutations in KCNA6 gene were found to be associated with early infantile epileptic phenotypes and neurodevelopmental anomalies. Functional characterization revealed that these mutations affect channel closure and voltage dependence. This study is the first to report the association between de novo variants in KCNA6 and neurological features.
Review
Biochemistry & Molecular Biology
Kirsten Bohmbach, Christian Henneberger, Johannes Hirrlinger
Summary: Learning and memory are complex functions of the brain that rely on multiple mechanisms. Recent experiments have shown that astrocytes, in addition to neurons, play a crucial role in these functions. However, the interaction between astrocytes and neurons is not well understood. This essay reviews current technologies for studying astrocytes in behaving animals, discusses astrocytic signaling mechanisms in learning and memory, and identifies gaps in our knowledge.
ESSAYS IN BIOCHEMISTRY
(2023)
Article
Cell Biology
Michael J. Devine, Blanka R. Szulc, Jack H. Howden, Guillermo Lopez-Domenech, Arnaud Ruiz, Josef T. Kittler
Summary: This study investigates the role of mitochondria in regulating synaptic transmission and plasticity. The results show that reducing mitochondrial Ca2+ uptake alters synaptic vesicle fusion and enhances long-term potentiation at specific synapses.
JOURNAL OF CELL SCIENCE
(2022)
Article
Biochemical Research Methods
Piotr Michaluk, Dmitri A. Rusakov
Summary: Population behavior of signaling molecules on the cell surface is crucial for their adaptive function. Fluorescent protein tagging has been used to understand this behavior, but it may overlook the process of in-out membrane recycling. The use of a pH-sensitive fluorescent tag allows for real-time monitoring of the dynamics of cell-surface molecules. This approach is demonstrated with the glial glutamate transporter GLT1, showing its recycling rate on the cell surface can be assessed.
Editorial Material
Neurosciences
Dmitri A. Rusakov
Summary: Fluorescent sensors of molecular activity have transformed our understanding of the brain. However, their signals only reflect the reaction between molecules rather than the activity itself. Thus, it is crucial to understand the sensor's characteristics to accurately interpret the results.
NATURE REVIEWS NEUROSCIENCE
(2022)
Article
Cell Biology
Cindy Brunskine, Stefan Passlick, Christian Henneberger
Summary: The concept of the tripartite synapse describes the close interaction between pre- and postsynaptic elements and the surrounding astrocyte processes. This study used super-resolution expansion microscopy to examine the organization of GABAergic synapses and nearby astrocytic processes. The findings indicate that astrocytic processes are less abundant near GABAergic synapses compared to glutamatergic synapses, and are more abundant at GABAergic synapses with large postsynaptic gephyrin clusters. These observations provide insights into the organization and function of synapses.
Article
Clinical Neurology
Nicola Masala, Martin Pofahl, Andre N. Haubrich, Khondker Ushna Sameen Islam, Negar Nikbakht, Maryam Pasdarnavab, Kirsten Bohmbach, Kunihiko Araki, Fateme Kamali, Christian Henneberger, Kurtulus Golcuk, Laura A. Ewell, Sandra Blaess, Tony Kelly, Heinz Beck
Summary: Masala et al. describe a mechanism involving Na+ channels that contributes to changes in hippocampal dendritic integration, degraded place coding, and deficits in spatial memory. Targeting this dendritic channelopathy pharmacologically may provide a new approach to enhance cognition in epilepsy.
Article
Cell Biology
Catia Domingos, Franziska E. Mueller, Stefan Passlick, Dagmar Wachten, Evgeni Ponimaskin, Martin K. Schwarz, Susanne Schoch, Andre Zeug, Christian Henneberger
Summary: The increase in RhoA activity leads to changes in astrocyte morphology, particularly the withdrawal of perisynaptic processes. These changes were replicated in vitro and in vivo, and overexpression of RhoA-CA specifically resulted in a significant reduction in fine peripheral astrocytic processes in vivo.
Article
Neurosciences
Aline Timmermann, Dario Tascio, Ronald Jabs, Anne Boehlen, Catia Domingos, Magdalena Skubal, Wenhui Huang, Frank Kirchhoff, Christian Henneberger, Andras Bilkei-Gorzo, Gerald Seifert, Christian Steinhaeuser
Summary: NG2 glia is a unique type of macroglial cells in the CNS that receive synaptic input from neurons. Dysfunction in NG2 glia has been found to improve spatial memory but has no effect on social memory. Loss of the K+ channel Kir4.1 in NG2 glia leads to enhanced synaptic depolarizations and expression of myelin basic protein in the hippocampus. Targeted deletion of the K+ channel in NG2 glia impairs long-term potentiation at CA3-CA1 synapses, which can be rescued by extracellular application of a TrkB receptor agonist. These findings highlight the importance of proper NG2 glia function in brain function and behavior.
Article
Cell Biology
Leonid P. Savtchenko, Dmitri A. Rusakov
Summary: Once released outside the synaptic cleft, the neurotransmitter glutamate binds quickly to its transporters on astroglial cells, limiting its excitatory transmission within synapses. However, there is growing evidence for glutamate's extrasynaptic actions, although the mechanisms and scope of these actions are still unclear. Our simulations support the concept of significant volume-transmitted actions of glutamate in the brain, with the unbinding of glutamate transporters playing an important role.
Article
Multidisciplinary Sciences
Olga Kopach, Sergyi Sylantyev, Lucie Bard, Piotr Michaluk, Janosch P. Heller, Ana Gutierrez del Arroyo, Gareth L. Ackland, Alexander V. Gourine, Dmitri A. Rusakov
Summary: Neutrophils, important white blood cells in acute inflammatory and adaptive immune responses, exhibit a swarming-pattern behavior controlled by calcium-dependent release of signaling molecules. This study found that stimulating one neutrophil can trigger a calcium signal and membrane current in neighboring neutrophils through an NMDA receptor. Additionally, glutamate released from neighboring neutrophils can induce glutamate release from neutrophils, providing evidence for positive-feedback inter-neutrophil communication.
Article
Multidisciplinary Sciences
Yichen Qiu, Nathanael O'Neill, Benito Maffei, Clara Zourray, Amanda Almacellas-Barbanoj, Jenna C. Carpenter, Steffan P. Jones, Marco Leite, Thomas J. Turner, Francisco C. Moreira, Albert Snowball, Tawfeeq Shekh-Ahmad, Vincent Magloire, Serena Barral, Manju A. Kurian, Matthew C. Walker, Stephanie Schorge, Dimitri M. Kullmann, Gabriele Lignani
Summary: The article presents a gene therapy strategy to down-regulate the excitability of overactive neurons in epilepsy models, leading to a persistent antiepileptic effect without interfering with normal behaviors.