Article
Cell Biology
Julien Louradour, Olivier Bortolotti, Eleonora Torre, Isabelle Bidaud, Ned Lamb, Anne Fernandez, Jean-Yves Le Guennec, Matteo E. Mangoni, Pietro Mesirca
Summary: This study reveals a novel role of Ca(v)1.3 channels in initiating and maintaining automaticity in dormant SANC upon beta-adrenergic stimulation.
Article
Biology
Elizabeth A. McCullagh, John Peacock, Alexandra Lucas, Shani Poleg, Nathaniel T. Greene, Addison Gaut, Samantha Lagestee, Yalan Zhang, Leonard K. Kaczmarek, Thomas J. Park, Daniel J. Tollin, Achim Klug
Summary: Naked mole-rats living underground have a specialized auditory system and show similar hearing onset to other rodents, but they have developmental differences in brain structure and morphology.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Josef Shin, Lora Kovacheva, Dominique Thomas, Strahinja Stojanovic, Christopher J. Knowlton, Johanna Mankel, Johannes Boehm, Navid Farassat, Carlos Paladini, Joerg Striessnig, Carmen C. Canavier, Gerd Geisslinger, Jochen Roeper
Summary: This study reveals the pacemaker function of the low-threshold L-type calcium channel Ca(v)1.3 in mice and demonstrates its role as a linear amplifier of firing rates for neuronal activity. It also provides evidence that the L-type channel inhibitor isradipine can selectively reduce the firing activity of vulnerable nigrostriatal DA SN neurons at therapeutic concentrations. These findings have important implications for the treatment of Parkinson's disease.
Article
Neurosciences
Samuel M. Young, Priyadharishini Veeraraghavan
Summary: In the auditory brainstem, reliable and precise synaptic transmission in response to action potential firing rates relies on the entry of Ca2+ through voltage-gated Ca2+ channels, with CaV2.1 playing a critical role. Understanding the mechanisms controlling the abundance and organization of CaV2.1 is essential for decoding sound information in auditory processing.
MOLECULAR AND CELLULAR NEUROSCIENCE
(2021)
Article
Allergy
Nicolas Giang, Marion Mars, Marc Moreau, Jose E. Mejia, Gregory Bouchaud, Antoine Magnan, Marine Michelet, Brice Ronsin, Geoffrey G. Murphy, Joerg Striessnig, Jean-Charles Guery, Lucette Pelletier, Magali Savignac
Summary: This study demonstrates that Ca(v)1.2 and Ca(v)1.3 in Th2 cells have non-redundant and synergistic functions, and deficiency in either one of these channels is sufficient to inhibit cardinal features of type 2 airway inflammation.
Article
Neurosciences
Natalia Hoshino, Yazan Altarshan, Ahmad Alzein, Amali M. Fernando, Hieu T. Nguyen, Emma F. Majewski, Vincent C. -F. Chen, M. William Rochlin, Wei-Ming Yu
Summary: The study revealed that Ephrin-A3 plays a crucial role in the formation of tonotopy in the auditory brainstem of mice. Lack of Ephrin-A3 leads to degradation of the tonotopic map and impairs detection of sound frequency changes.
JOURNAL OF COMPARATIVE NEUROLOGY
(2021)
Article
Biology
Sudha Rajderkar, Iros Barozzi, Yiwen Zhu, Rong Hu, Yanxiao Zhang, Bin Li, Ana Alcaina Caro, Yoko Fukuda-Yuzawa, Guy Kelman, Adyam Akeza, Matthew J. Blow, Quan Pham, Anne N. Harrington, Janeth Godoy, Eman M. Meky, Kianna von Maydell, Riana D. Hunter, Jennifer A. Akiyama, Catherine S. Novak, Ingrid Plajzer-Frick, Veena Afzal, Stella Tran, Javier Lopez-Rios, Michael E. Talkowski, K. C. Kent Lloyd, Bing Ren, Diane E. Dickel, Axel Visel, Len A. Pennacchio
Summary: Topologically associating domain (TAD) boundaries partition the genome and disruptions of these boundaries can interfere with normal gene expression and cause developmental phenotypes. In this study, targeted deletions of TAD boundaries in mice resulted in phenotypic changes, including altered chromatin interactions, gene expression, viability, and anatomical phenotypes. These findings emphasize the importance of TAD boundary sequences for proper genome function and the need to consider the potential pathogenicity of noncoding deletions affecting TAD boundaries in clinical genetics screening.
COMMUNICATIONS BIOLOGY
(2023)
Article
Neurosciences
Stefanie Krinner, Friederike Predoehl, Dinah Burfeind, Christian Vogl, Tobias Moser
Summary: Afferent synapses between inner hair cells and spiral ganglion neurons rely on Rab3 interacting molecule-binding proteins (RIM-BPs) for normal sound encoding, with RIM-BP2 playing a leading role. Genetic disruption of RIM-BP1 and 2 causes more severe hearing impairment compared to just RIM-BP2 disruption, pointing to the crucial role of these proteins in synaptic function.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Hui Wang, Mingqi Xie, Giorgio Rizzi, Xin Li, Kelly Tan, Martin Fussenegger
Summary: Parkinson's disease (PD) is primarily caused by excessive activity-related Ca2+ oscillations, resulting in the selective loss of substantia nigra dopaminergic neurons. In this study, a synthetic-biology-inspired drug-discovery platform was used to identify potential PD drugs. Through virtual screening and deep-learning neural networks, the compound sclareol was identified as a promising candidate for PD pharmacotherapy. In vitro and in vivo experiments confirmed that sclareol selectively inhibits Ca(v)1.3, reduces the firing response of SNc DA neurons, and protects against DA neuronal loss and motor impairment in a mouse model of PD.
Article
Neurosciences
Brenda Rocamonde, Vicente Herranz-Perez, Jose Manuel Garcia-Verdugo, Emmanuelle Huillard
Summary: Ependymal cells, derived from radial glia, are crucial for proper cerebrospinal fluid flow and neurogenesis modulation. The transcriptional regulator ID4 plays a significant role in the development and maturation of ependymal cells.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Juan J. Ferreira, Adriana Cassina, Pilar Irigoyen, Mariana Ford, Santiago Pietroroia, Nikita Peramsetty, Rafael Radi, Celia M. Santi, Rossana Sapiro
Summary: The calcium influx through the CatSper channel during capacitation increases mitochondrial activity in sperm, which is essential for sperm hyperactivation and fertilization. This novel mechanism discovered in this study may lead to new molecular targets for fertility treatments and male contraception.
Article
Plant Sciences
Ryoya Okawa, Yoko Hayashi, Yasuko Yamashita, Yoshikatsu Matsubayashi, Mari Ogawa-Ohnishi
Summary: This study highlights the importance of arabinogalactan proteins (AGPs) in the regulation of plasmodesmata structure and cell wall properties in Arabidopsis.
Article
Neurosciences
Rose Rizzi, Gavin M. Bidelman
Summary: In this study, brainstem responses to fused speech percepts were investigated using frequency-following responses (FFRs). The results showed that FFRs can reflect the neural activity of fused speech perception and phonetic categories. Behavioral tests confirmed that listeners could categorize dichotic speech tokens, indicating they were heard with a fused phonetic percept. This study suggests that FFRs contain binaurally integrated, category-level information in human brainstem processing.
Article
Neurosciences
Lizbeth Grimaldo, Alejandro Sandoval, Paz Duran, Liliana Gomez Flores-Ramos, Ricardo Felix
Summary: This study investigates the degradation mechanisms of neuronal CaV1.3 channels by Parkin and suggests that Parkin promotes proteasomal degradation of CaV1.3, which may be relevant to the pathophysiology of Parkinson's disease.
JOURNAL OF NEUROPHYSIOLOGY
(2022)
Article
Physiology
Emil Rindom, Jon Herskind, Bert Blaauw, Kristian Overgaard, Kristian Vissing, Frank de Paoli
Summary: The study suggests that exercise-induced increases in protein synthesis and transcriptional signaling depend on the combined effect of excitation and tension development, while signaling for translation initiation is solely dependent on tension development itself.
Article
Allergy
Nicolas Giang, Marion Mars, Marc Moreau, Jose E. Mejia, Gregory Bouchaud, Antoine Magnan, Marine Michelet, Brice Ronsin, Geoffrey G. Murphy, Joerg Striessnig, Jean-Charles Guery, Lucette Pelletier, Magali Savignac
Summary: This study demonstrates that Ca(v)1.2 and Ca(v)1.3 in Th2 cells have non-redundant and synergistic functions, and deficiency in either one of these channels is sufficient to inhibit cardinal features of type 2 airway inflammation.
Article
Cell Biology
Marlena Herbertz, Soenke Harder, Hartmut Schlueter, Christian Lohr, Susanne Dobler
Summary: This study revealed the distribution and composition of Na,K-ATPase alpha 1/ss complexes in the nervous tissue of the milkweed bug, challenging the current understanding that the alpha 1 and ss subunits must associate to form functional complexes.
CELL AND TISSUE RESEARCH
(2022)
Article
Neurosciences
Nicolas I. C. Muller, Isabelle Paulussen, Lina N. Hofmann, Jonas O. Fisch, Abhyudai Singh, Eckhard Friauf
Summary: Sound localization involves information analysis in the lateral superior olive (LSO), a conspicuous nucleus in the mammalian auditory brainstem. This study shows that acoustic experience plays a significant role in the development of reliable neurotransmission in the LSO, which is essential for effective interaural level difference (ILD) detection.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Editorial Material
Neurosciences
Enrica Boda, Francesca Boscia, Christian Lohr
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Brenna C. Fearey, Lars Binkle, Daniel Mensching, Christian Schulze, Christian Lohr, Manuel A. Friese, Thomas G. Oertner, Christine E. Gee
Summary: The TRPM4 channel has been found to play a significant role in disease severity in multiple sclerosis and neuronal cell death in brain injury. It was discovered that TRPM4 does not significantly affect basal hippocampal synaptic transmission but does contribute to excitatory postsynaptic responses in the acute phase of EAE in a glibenclamide-sensitive manner.
SCIENTIFIC REPORTS
(2022)
Article
Clinical Neurology
Jakob Matschke, Henri Lahann, Susanne Krasemann, Hermann Altmeppen, Susanne Pfefferle, Giovanna Galliciotti, Antonia Fitzek, Jan-Peter Sperhake, Benjamin Ondruschka, Miriam Busch, Natalie Rotermund, Kristina Schulz, Christian Lohr, Matthias Dottermusch, Markus Glatzel
Summary: The mechanism of how SARS-CoV-2 infection leads to brain damage is still not clear. This study found that the degree of immune cell activation in COVID-19 patients is related to age, while the degree of reactive astrogliosis is age-dependent but not influenced by COVID-19.
FRONTIERS IN NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Josef Shin, Lora Kovacheva, Dominique Thomas, Strahinja Stojanovic, Christopher J. Knowlton, Johanna Mankel, Johannes Boehm, Navid Farassat, Carlos Paladini, Joerg Striessnig, Carmen C. Canavier, Gerd Geisslinger, Jochen Roeper
Summary: This study reveals the pacemaker function of the low-threshold L-type calcium channel Ca(v)1.3 in mice and demonstrates its role as a linear amplifier of firing rates for neuronal activity. It also provides evidence that the L-type channel inhibitor isradipine can selectively reduce the firing activity of vulnerable nigrostriatal DA SN neurons at therapeutic concentrations. These findings have important implications for the treatment of Parkinson's disease.
Article
Biochemistry & Molecular Biology
Ferenc Torok, Kamer Tezcan, Ludovica Filippini, Monica L. Fernandez-Quintero, Lucia Zanetti, Klaus R. Liedl, Raphaela S. Drexel, Joerg Striessnig, Nadine J. Ortner
Summary: Germline gain-of-function missense variants in the CACNA1D gene can cause severe neurodevelopmental disorders with or without endocrine symptoms. We report a 4-week-old newborn with a novel de novo missense variant F747S in the Cav1.3 alpha 1-subunit, which is associated with a prominent jittering phenotype, developmental delay, elevated aldosterone level, and transient hypoglycemia. Functional experiments confirmed the pathogenicity of the variant and revealed significant changes in channel gating. The increased sensitivity to the L-type Ca2+ channel blocker isradipine suggests its potential as a treatment option for carriers of this mutation.
HUMAN MOLECULAR GENETICS
(2023)
Article
Entomology
Marlena Herbertz, Jennifer Lohr, Christian Lohr, Susanne Dobler
Summary: The study explores the importance of beta-subunits in cell functionality and their tissue-specific distribution. The findings reveal that knockdown of different beta-subunits significantly disrupts molting and results in weakened phenotypes. Furthermore, the study suggests the existence of standalone beta-subunits and their structure-specific distribution, indicating potential pump-independent functions.
Article
Neurosciences
Christian Lohr
Summary: This review summarizes the function of P2Y receptors in astrocytes, including their regulation of cellular functions and involvement in various brain diseases.
Article
Biochemistry & Molecular Biology
Simon L. Wadle, Tatjana T. X. Schmitt, Jutta Engel, Simone Kurt, Jan J. Hirtz
Summary: Loss of the alpha(2)delta 3 auxiliary subunit leads to an inability to distinguish amplitude-modulated tones and has been associated with autism spectrum disorder. Analysis of neuronal activity in the auditory cortex reveals subfield-specific alterations, with higher subfields showing more well-tuned neurons and lower local heterogeneity.
BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Susanne Rinne, Birgit Stallmeyer, Alexandra Pinggera, Michael F. Netter, Lina A. Matschke, Sven Dittmann, Uwe Kirchhefer, Ulrich Neudorf, Joachim Opp, Joerg Striessnig, Niels Decher, Eric Schulze-Bahr
Summary: Cav1.3 voltage-gated L-type calcium channels are associated with various clinical symptoms, such as cardiac pacemaking, hearing, hormone secretion, epilepsy, autism, intellectual disability, and ADHD. This study identified a genetic variant in the CACNA1D gene that was associated with a syndromal phenotype of sinus node dysfunction, epilepsy, and ADHD in a three-generation family. Functional studies revealed that the variant induced isoform-specific alterations in Cav1.3 channel function, leading to the combined clinical symptoms observed in the family.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Fatemeh Hassani Nia, Daniel Woike, Isabel Bento, Stephan Niebling, Debora Tibbe, Kristina Schulz, Daniela Hirnet, Matilda Skiba, Hans-Hinrich Hoenck, Katharina Veith, Christian Guenther, Tasja Scholz, Tatjana Bierhals, Joenna Driemeyer, Renee Bend, Antonio Virgilio Failla, Christian Lohr, Maria Garcia Alai, Hans-Juergen Kreienkamp
Summary: This study investigates the impact of two mutations in the SHANK2 gene on neurodevelopment. The results show that these mutations disrupt the interactions of Shank2 with other proteins, leading to abnormal assembly of postsynaptic protein complexes into nanoclusters. This interference affects the positioning of neurons and synaptic transmission, ultimately impacting normal brain development in humans.
MOLECULAR PSYCHIATRY
(2022)
Review
Pharmacology & Pharmacy
Ludovica Filippini, Nadine J. J. Ortner, Teresa Kaserer, Jorg Striessnig
Summary: Voltage-gated L-type Ca2+-channels, especially Ca(v)1.3 subtype, are potential drug targets for the treatment of various diseases. However, the selectivity of Ca(v)1.3-selective blockers remains controversial, and there are no suitable pharmacological tools to confirm or refute the role of Ca(v)1.3 channels in cellular responses. Essential criteria for a small molecule to be considered Ca(v)1.3-selective are suggested.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biology
Omar A. Hafez, Benjamin Escribano, Rouven L. Ziegler, Jan J. Hirtz, Ernst Niebur, Jan Pielage
Summary: The ability to associate neutral stimuli with valence information and store them as memories is crucial for decision making. A computational model of the central decision module in the Drosophila mushroom body was built, incorporating the architecture of one output neuron, synaptic connectivity of its presynaptic cells, and membrane properties. This model showed that the neuron efficiently controls and modulates its activity in response to learning, allowing for storage of large numbers of memories.