The evolution of novel motor behaviors requires modifications in the central pattern generators (CPGs) controlling muscle activity. How such changes gradually lead to novel behaviors remains enigmatic due to the long time course of evolution. Rattlesnakes provide a unique opportunity to investigate how a locomotor CPG was evolutionarily modified to generate a novel behavior-in this case, acoustic signaling. We show that motoneurons (MNs) in the body and tail spinal cord of rattlesnakes possess fundamentally different physiological characteristics, which allow MNs in the tail to integrate and transmit CPG output for controlling superfast muscles with high temporal precision. Using patch-clamp electrophysiology, we demonstrate that these differences in locomotor and rattle MNs are mainly determined by KV7 potassium channels. However, although KV7 exerted a significantly different influence on locomotor and rattle MN physiology, single-cell RNA-seq unexpectedly did not reveal any differences in KV7 channels' expression. VIDEO ABSTRACT.
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http://dx.doi.org/10.1016/j.cub.2023.11.062 | DOI Listing |
Neurobiol Dis
December 2024
The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052, Australia. Electronic address:
Background: Developmental and epileptic encephalopathies (DEE) are rare but severe neurodevelopmental disorders characterised by early-onset seizures often combined with developmental delay, behavioural and cognitive deficits. Treatment for DEEs is currently limited to seizure control and provides no benefits to the patients' developmental and cognitive outcomes. Genetic variants are the most common cause of DEE with KCNQ2 being one of the most frequently identified disease-causing genes.
View Article and Find Full Text PDFBr J Pharmacol
December 2024
Department of Neurophysiology and Neuropharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Background And Purpose: Paracetamol has been found to alleviate inflammatory pain by modulating K7 channels. Its metabolite N-acetyl-4-benzoquinoneimine (NAPQI) increases currents through these channels via a stretch of three cysteine residues in the channel S2-S3 linker. Through this effect, the excitability of neurons in the pain pathway is dampened.
View Article and Find Full Text PDFNeuropharmacology
February 2025
Department of Neuroscience, Universidad Central del Caribe, Bayamón, PR, 00956, USA. Electronic address:
Gulf War Illness (GWI) has been consistently linked to exposure to pyridostigmine (PB), N,N-Diethyl-meta-toluamide (DEET), permethrin (PER), and traces of sarin. In this study, diisopropylfluorophosphate (DFP, sarin surrogate) and the GWI-related chemicals were found to reduce the number of functionally active neurons in rat hippocampal slices. These findings confirm a link between GWI neurotoxicants and N-Methyl-D-Aspartate (NMDA)-mediated excitotoxicity, which was successfully reversed by Edelfosine (a phospholipase Cβ (PLCβ3) inhibitor) and Flupirtine (a Kv7 channel agonist).
View Article and Find Full Text PDFVascul Pharmacol
September 2024
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Kralove, Czech Republic. Electronic address:
Substituted catechols include both natural and synthetic compounds found in the environment and foods. Some of them are flavonoid metabolites formed by the gut microbiota which are absorbed afterwards. Our previous findings showed that one of these metabolites, 4-methylcatechol, exerts potent vasorelaxant effects in rats.
View Article and Find Full Text PDFBrain Behav Immun
November 2024
Institute of Physiology I, University of Münster, Münster, Germany. Electronic address:
Background: Multiple Sclerosis (MS) is an autoimmune neurodegenerative disease, whose primary hallmark is the occurrence of inflammatory lesions in white and grey matter structures. Increasing evidence in MS patients and respective murine models reported an impaired ionic homeostasis driven by inflammatory-demyelination, thereby profoundly affecting signal propagation. However, the impact of a focal inflammatory lesion on single-cell and network functionality has hitherto not been fully elucidated.
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