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How breathing is generated by the preBötzinger Complex (preBötC) remains divided between two ideological frameworks, and the persistent sodium current () lies at the heart of this debate. Although is widely expressed, the considers it essential because it endows a small subset of neurons with intrinsic bursting or "pacemaker" activity. In contrast, considers dispensable because rhythm emerges from "pre-inspiratory" spiking activity driven by feed-forward network interactions. Using computational modeling, we discover that changes in spike shape can dissociate from intrinsic bursting. Consistent with many experimental benchmarks, conditional effects on spike shape during simulated changes in oxygenation, development, extracellular potassium, and temperature alter the prevalence of intrinsic bursting and pre-inspiratory spiking without altering the role of . Our results support a unifying hypothesis where and excitatory network interactions, but not intrinsic bursting or pre-inspiratory spiking, are critical interdependent features of preBötC rhythmogenesis.
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http://dx.doi.org/10.1101/2023.10.30.564834 | DOI Listing |
Cell Rep
September 2025
Department of Biochemistry, University of Colorado, Boulder, CO 80303, USA. Electronic address:
RNA polymerase II (RNAPII) is regulated by sequence-specific transcription factors (TFs) and the pre-initiation complex (PIC): TFIIA, TFIIB, TFIID, TFIIE, TFIIF, TFIIH, and Mediator. TFs, Mediator, and RNAPII contain intrinsically disordered regions (IDRs) and form phase-separated condensates, but how IDRs control RNAPII function remains poorly understood. Using purified PIC factors, we developed a real-time in vitro fluorescence transcription (RIFT) assay for second-by-second visualization of transcription at hundreds of promoters simultaneously.
View Article and Find Full Text PDFExp Physiol
September 2025
Department of Neurology, Dell Medical School at The University of Texas at Austin, Austin, Texas, USA.
The neurodevelopmental disorder fragile X syndrome (FXS) results from hypermethylation of the FMR1 gene, which prevents production of the FMRP protein. FMRP modulates the expression and function of a variety of proteins, including voltage-gated ion channels, such as hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels, which are integral to rhythmic activity in thalamic structures. Thalamocortical pathology, particularly involving the mediodorsal thalamus (MD), has been implicated in neurodevelopmental disorders such as FXS.
View Article and Find Full Text PDFEntropy (Basel)
August 2025
Institute of Humanities, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Nagano, Japan.
The dynamics of signal transmission in neuronal networks remain incompletely understood. In this study, we propose a novel Rulkov neuronal network model that incorporates Q-learning, a reinforcement learning method, to establish efficient signal transmission pathways. Using a simulated neuronal network, we focused on a key parameter that modulates both the intrinsic dynamics of individual neurons and the input signals received from active neighbors.
View Article and Find Full Text PDFSci Adv
August 2025
Department of Materials Science and Engineering, University of California, Los Angeles, CA 90095, USA.
Photoactivated drug delivery is a promising therapeutic strategy that enables spatial and temporal control of payload release. A critical component of this approach is the photoresponsive material that has sufficient drug-loading capacity and can be actuated by near-infrared (NIR) light with considerable penetration depths. Here, we establish a photoactivated drug delivery platform based on the π-stacked organic framework (πOF), which demonstrates an intrinsic NIR absorption and superior photothermal effect.
View Article and Find Full Text PDFFront Immunol
August 2025
Morgridge Institute for Research, Madison, WI, United States.
Introduction: Neutrophils are critical innate immune cells that heterogeneously respond to infection and inflammation by performing functions such as oxidative burst and NETosis, which require significant metabolic adaptation. Deeper insights into the single cell diversity of such metabolic changes will help identify regulation of neutrophil functions in health and diseases. Due to their short lifespan and associated technical challenges, the early metabolic processes of neutrophil activation are not completely understood.
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