Article
Biology
Peter R. Strege, Luke M. Cowan, Constanza Alcaino, Amelia Mazzone, Christopher A. Ahern, Lorin S. Milescu, Gianrico Farrugia, Arthur Beyder
Summary: Shear stress and patch suction can reversibly alter the kinetic properties and maximum current of NaChBac, suggesting it is mechanosensitive. Structural analysis reveals a large displacement of the intracellular gate, supporting the proposed mechanosensitive mechanism.
Article
Chemistry, Medicinal
Juan Antonio Contreras Vite, Carlos Vega Valle, Happi Biekeu Mbem, Sarah-Maude Boivin, Robert Dumaine
Summary: Lamotrigine is commonly used for treating bipolar disorder and epilepsy. The US FDA has recently issued a warning regarding the drug's potential to cause conduction anomalies and Brugada syndrome in epileptic patients. In this study, researchers used patch clamp technique on rat cardiomyocytes to investigate the effect of Lamotrigine on cardiac sodium current (I-Na). The results showed that Lamotrigine inhibited I-Na peak amplitude, reduced cardiac excitability, and prolonged the action potential refractory period in epileptic rats.
Article
Biochemistry & Molecular Biology
Anita Monteverdi, Danila Di Domenico, Egidio D'Angelo, Lisa Mapelli
Summary: In this study, the frequency dependence and spatial anisotropy of cerebellar activation were investigated using a high-throughput high-density multielectrode array. The results showed that mossy fiber inputs reached the Purkinje cell layer even at low frequencies, but the efficiency of transmission increased at higher frequencies. These findings provide important insights into the computational properties and pathological alterations of the cerebellar cortex.
Article
Biochemistry & Molecular Biology
Karl Josef Foehr, Michael Rapp, Michael Fauler, Thomas Zimmer, Bettina Jungwirth, David Alexander Christian Messerer
Summary: Aripiprazole has been identified as a potent blocker of the dominant voltage-gated sodium channel of heart muscle. Its interactions with the channel differ depending on the state, with weaker affinity for the resting state and stronger affinity for the inactivated state.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Damian C. Bell, Luigi Leanza, Saverio Gentile, Daniel R. Sauter
Summary: Ion channels play key roles in various physiological processes, and their dysfunction can lead to channelopathies, including cancer. The field of ion channel and cancer research has rapidly grown in the past two decades, allowing us to gain deeper insights into the mechanisms of ion channels in cancer and develop therapeutic interventions.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Gastroenterology & Hepatology
Zhiling Li, Werend Boesmans, Youcef Kazwiny, Marlene M. Hao, Pieter Vanden Berghe
Summary: Live calcium imaging is a valuable tool for simultaneous analysis of neuronal activity. This study investigated how enteric neurons respond to different modes of depolarization using electrophysiology and calcium imaging techniques. The research found that single action potentials can elicit calcium transients in both AH-neurons and S-neurons, and nicotinic acetylcholine receptor stimulation can be used to distinguish between these two classes.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Anesthesiology
Tyler J. Browne, Kelly M. Smith, Mark A. Gradwell, Jacqueline A. Iredale, Christopher V. Dayas, Robert J. Callister, David I. Hughes, Brett A. Graham
Summary: Projection neurons in the spinal dorsal horn play a crucial role in relaying sensory information to higher brain centres, receiving inputs from the periphery, brain, and local circuits. Recent studies in transgenic mice have provided insights into dorsal horn circuitry, while information on projection neurons is mainly based on previous studies in monkey, cat, and rat. The study on mouse spinoparabrachial projection neurons identified distinct subpopulations in lamina I based on electrophysiological properties, suggesting different sensory signalling features. Additionally, the research revealed novel information on deeper lamina SPBNs, showing different sensory codes destined for the PBN and their contribution to excitatory input in dorsal horn circuits.
Article
Cell Biology
Adam Feher, Marianna Pocsi, Ferenc Papp, Tibor G. Szanto, Agota Csoti, Zsolt Fejes, Bela Nagy, Balazs Nemes, Zoltan Varga
Summary: This study identified multiple voltage-gated sodium channels in the plasma membrane of human B cells using electrophysiological and molecular biology methods. The detected sodium currents showed sensitivity between TTX-sensitive and TTX-insensitive channels, suggesting the co-existence of multiple Na(V)1 subtypes. The results also supported the functional role of these channels in shaping and maintaining the resting membrane potential.
Article
Neurosciences
Aleksandar Rakovic, Dorothea Voss, Franca Vulinovic, Britta Meier, Ann-Katrin Hellberg, Carla Nau, Christine Klein, Enrico Leipold
Summary: Induced pluripotent stem cells can be used to create patient-specific in vitro models for studying Parkinson's disease and drug screening. However, current differentiation methods result in heterogeneous cell populations with low fractions of relevant dopaminergic neurons. This study utilized CRISPR/Cas9 technology to generate a reporter iPSC line and compared different differentiation protocols. The floor plate protocol was found to be the most efficient in generating electrophysiologically mature dopaminergic neurons.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Walter Francesconi, Fulvia Berton, Valentina Olivera-Pasilio, Joanna Dabrowska
Summary: The study reveals that oxytocin has distinct effects on different types of neurons in the dorsolateral bed nucleus of the stria terminalis. It selectively excites some neurons while inhibiting others, potentially facilitating conditioned fear by suppressing inter-neuronal interactions.
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
Biochemical Research Methods
Christopher Miranda, Madeleine R. Howell, Joel F. Lusk, Ethan Marschall, Jarrett Eshima, Trent Anderson, Barbara S. Smith
Summary: This study demonstrates a method of guiding glass micropipette electrodes to neurons by collecting fluorescence at the aperture using an intra-electrode tapered optical fiber. The use of a tapered fiber for excitation and collection of fluorescence at the micropipette tip allows for targeted robotic approach to labeled neurons independent of microscopy.
BIOMEDICAL OPTICS EXPRESS
(2021)
Review
Neurosciences
Meike E. van der Heijden, Roy V. Sillitoe
Summary: Cerebellar development is a complex process involving interactions between inhibitory Purkinje cells and excitatory granule cells, with Purkinje cells considered as master regulators of the process. The connectivity and function of Purkinje cells are influenced by cues provided by granule cells, which help shape the firing properties of Purkinje cells. This dynamic interplay between different cell types is essential for the establishment of mature cerebellar circuits.
Article
Neurosciences
Marcela Lipovsek, Cedric Bardy, Cathryn R. Cadwell, Kristen Hadley, Dmitry Kobak, Shreejoy J. Tripathy
Summary: Patch-seq is a revolutionary technique in neuroscience that integrates morphology, physiology, and gene expression data to study neuronal biology comprehensively. It enables targeted study of specific neuronal populations, compilation of multimodal cell type atlases, and investigation of the molecular basis of morphologic and functional diversity. This technique has the potential for further technical development and implementation in various research areas to directly link gene expression to brain function.
JOURNAL OF NEUROSCIENCE
(2021)
Review
Pharmacology & Pharmacy
Shirin Ahmadi, Melisa Benard-Valle, Kim Boddum, Fernanda C. Cardoso, Glenn F. King, Andreas Hougaard Laustsen, Anne Ljungars
Summary: Ion channels are crucial for various physiological processes. Venomous creatures exploit ion channels by producing toxins that target them, leading to dysregulation which can cause severe complications in humans. However, the discovery of selective venom toxins has contributed to the development of drugs for envenoming and ion channel-related diseases.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Neurosciences
Joanne Falck, Christine Bruns, Sheila Hoffmann-Conaway, Isabelle Straub, Erik J. Plautz, Marta Orlando, Humaira Munawar, Marion Rivalan, York Winter, Zsuzsanna Izsvak, Dietmar Schmitz, F. Kent Hamra, Stefan Hallermann, Craig Curtis Garner, Frauke Ackermann
JOURNAL OF NEUROSCIENCE
(2020)
Article
Biology
Isabelle Straub, Laurens Witter, Abdelmoneim Eshra, Miriam Hoidis, Niklas Byczkowicz, Sebastian Maas, Igor Delvendahl, Kevin Dorgans, Elise Savier, Ingo Bechmann, Martin Krueger, Philippe Isope, Stefan Hallermann
Review
Pharmacology & Pharmacy
Josefine Sell, Holger Haselmann, Stefan Hallermann, Michael Hust, Christian Geis
Summary: Current treatment for antibody-mediated encephalitides (AE) includes escalating immunotherapy strategies such as plasma exchange, steroid application, and B cell depletion. While effective in many patients, specific immunotherapy combined with supportive target-specific therapy may provide faster control of severe symptoms, shorten the disease course, and lead to long-lasting disease stability. Novel therapeutic approaches, such as modulation of targeted receptors by small molecules crossing the blood-brain barrier and prevention of antibody binding, show promise for the future treatment of AE.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2021)
Article
Cell Biology
Andreas Ritzau-Jost, Timur Tsintsadze, Martin Krueger, Jonas Ader, Ingo Bechmann, Jens Eilers, Boris Barbour, Stephen M. Smith, Stefan Hallermann
Summary: The study shows distinct properties and dynamics of presynaptic action potential spikes in pyramidal neurons and inhibitory interneurons in the neocortex, indicating fundamental differences between excitatory and inhibitory boutons.
Article
Biology
Katarzyna Kita, Catarina Albergaria, Ana S. Machado, Megan R. Carey, Martin Muller, Igor Delvendahl
Summary: GluA4 plays a crucial role in synaptic excitation and associative memory formation in the cerebellum, with its deletion causing reduced synaptic transmission and impaired granule cell coding, leading to deficits in associative learning.
Article
Biology
Abdelmoneim Eshra, Hartmut Schmidt, Jens Eilers, Stefan Hallermann
Summary: The basal free Ca2+ concentration critically controls action potential-evoked release, indicating a high-affinity Ca2+ sensor for vesicle priming. There is a surprisingly shallow and non-saturating relationship between release rate and intracellular Ca2+ concentration up to 50 μM. The rate of vesicle replenishment during sustained elevated intracellular Ca2+ concentration exhibited little Ca2+-dependence.
Article
Multidisciplinary Sciences
Changliang Liu, Xintong Cai, Andreas Ritzau-Jost, Paul F. Kramer, Yulong Li, Zayd M. Khaliq, Stefan Hallermann, Pascal S. Kaeser
Summary: Information flow in neurons involves integration of inputs in dendrites, generation of action potentials near the soma, and release of neurotransmitters from nerve terminals in the axon. A study found that acetylcholine-releasing neurons in the striatum can induce action potential firing in distal dopamine axons. This mechanism segregates the control of dopamine signaling between axons and somata.
Article
Neurosciences
Jannik M. Buettner, Leonie Sowoidnich, Florian Gerstner, Beatriz Blanco-Redondo, Stefan Hallermann, Christian M. Simon
Summary: The activation of the p53 pathway is associated with neuronal degeneration in various neurological disorders, including SMA. Aberrant expression of p53 leads to the selective death of motor neurons in SMA. In this study, the expression of p53 downstream targets c-fos, perp, and fas was investigated in vulnerable motor neurons of SMA mice. Nuclear upregulation of c-Fos protein was observed in degenerating motor neurons in different mouse models of SMA, suggesting that it may serve as a readout for therapeutic approaches targeting neuronal death in SMA and other p53-dependent neurodegenerative diseases.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Clinical Neurology
Stephan Steinke, Toni Kirmann, Eleonora A. Loi, Jana Nerlich, Iron Weichard, Philipp Kuhn, Torsten Bullmann, Andreas Ritzau-Jost, Filiz Sila Rizalar, Harald Pruess, Volker Haucke, Christian Geis, Michael Hust, Stefan Hallermann
Summary: Researchers developed and validated a construct that can neutralize autoantibodies from patients with NMDAR encephalitis, preventing receptor internalization and memory deficits in a mouse model. This approach offers a promising strategy for fast and specific treatment of NMDAR encephalitis.
Article
Biochemistry & Molecular Biology
R. Asadollahi, I Delvendahl, R. Muff, G. Tan, D. G. Rodrieguez, S. Turan, M. Russo, B. Oneda, P. Joset, P. Boonsawat, R. Masood, M. Mocera, I. Ivanovski, A. Baumer, R. Bachmann-Gagescu, R. Schlapbach, H. Rehrauer, K. Steindl, A. Begemann, A. Reis, J. Winkler, B. Winner, M. Mueller, A. Rauch
Summary: Pathogenic variants in SCN2A cause epilepsy or intellectual disability/autism. We investigated iPSC-derived neurons from patients with diverse SCN2A variants and found that ID neurons had lower Na(V)1.2 levels and impaired sodium current density, while epilepsy neurons showed impaired sodium channel inactivation. Single-cell transcriptomics revealed dysregulation of specific molecular pathways in both types of neurons.
HUMAN MOLECULAR GENETICS
(2023)
Article
Neurosciences
Magdalena Wender, Grit Bornschein, Simone Brachtendorf, Stefan Hallermann, Jens Eilers, Hartmut Schmidt
Summary: The composition of voltage-gated Ca2+ channel subtypes changes during the development of CNS synapses. Cav2.2 and Cav2.3 lose their function in gating evoked release during postnatal synapse maturation. Cav2.1 currents provide the almost exclusive trigger for evoked release in mature boutons, while Cav2.3 currents are required for presynaptic long-term potentiation. The functional significance of Cav2.2 in mature boutons remained elusive, but it was found to significantly boost vesicle recruitment during sustained high-frequency synaptic transmission.
JOURNAL OF NEUROSCIENCE
(2023)
Editorial Material
Neurosciences
Igor Delvendahl, Bo Hu, Jonathan G. Murphy
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Biochemical Research Methods
Andreas Ritzau-Jost, Jana Nerlich, Thomas Kaas, Boris Barbour, Martin Krueger, Timur Tsintsadze, Jens Eilers, Stephen M. Smith, Stefan Hallermann
Summary: This article provides a protocol for direct whole-cell patch-clamp recordings from small presynaptic boutons of primary dissociated cultured neurons of the rodent neocortex.
Article
Biochemical Research Methods
Camille Gontier, Simone Carlo Surace, Igor Delvendahl, Martin Mueller, Jean-Pascal Pfister
Summary: Bayesian Active Learning (BAL) is an efficient framework for learning model parameters by maximizing the mutual information between observations and unknown parameters. However, its applicability to real-time experiments is limited due to high-dimensional integrations and optimizations. To address this issue, we propose an Efficient Sampling-Based Bayesian Active Learning (ESB-BAL) framework that can be used in real-time biological experiments. We demonstrate the effectiveness of our method in improving the precision of model-based inferences for estimating chemical synapse parameters, paving the way for more systematic and efficient experimental designs in physiology.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Biochemical Research Methods
Jannik M. Buettner, Toni Kirmann, George Z. Mentis, Stefan Hallermann, Christian M. Simon
Summary: This article describes a new method for analyzing spinal premotor synapses, which enables in-depth study of pathological changes in these synapses during neurodegeneration using confocal and STED imaging, as well as analysis by confocal microscopy.