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Meents, J.

Publications and source records attributed to Meents, J..

2 recordsLinked to original sources

Large-scale infra-slow dynamics of extracellular potentials linked to synchronous states revealed by graphene neural probes

Infra-slow (<0.5 Hz) brain dynamics reflect homeostatic and neuromodulatory processes that modulate neuronal excitability and shape faster oscillations across brain regions. Infra-slow brain activity is typically inferred from magnetic or optical imaging, but these methods are limited in temporal resolution and compatibility with unconstrained behavior. Infra-slow local field potentials (isLFPs) could provide a direct measure of infra-slow network dynamics, but have remained poorly characterized due to the absence of scalable, DC-coupled recording methods. Here, we introduce DC-coupled electrophysiological imaging based on arrays of up to 512 multiplexed graphene transistors enabling stable, high-density recordings across cortical regions and cortical layers in freely moving rats. We developed an analytical framework for the analysis of wide-band LFP, revealing that synchronous oscillatory states of variable duration and spatial scale are consistently linked to topographically and translaminarly structured DC potential shifts. We propose a physiological model linking these DC shifts to sustained gradients of extracellular K+ concentration, providing a mechanistic connection between neuronal synchrony and isLFP dynamics. By integrating DC-coupled sensing, multiplexed scalability, and depth-surface co-registration, this work establishes a new modality for imaging-like electrophysiology in freely moving animals and a framework for interpreting infra-slow dynamics.

neuroscience↗

Uncoupling sodium channel dimers rescues phenotype of pain-linked Nav1.7 mutation

The voltage-gated sodium channel Nav1.7 is essential for an adequate perception of painful stimuli. Its mutations cause various pain syndromes in human patients. The hNav1.7/A1632E mutation induces symptoms of erythromelalgia and paroxysmal extreme pain disorder (PEPD), and its main gating change is a strongly enhanced persistent current.\n\nUsing molecular simulations, we demonstrate that the disease causing persistent current of hNav1.7/A1632E is due to impaired binding of the IFM motif, thus affecting proper function of the recently proposed allosteric fast inactivation mechanism. By using native polyacrylamide gel electrophoresis (PAGE) gels, we show that hNav1.7 dimerizes. The disease-linked persistent current depends on the channels functional dimerization status: Using difopein, a 14-3-3 inhibitor known to uncouple dimerization of hNav1.5, we detect a significant decrease in hNav1.7/A1632E induced persistent currents.\n\nOur work identifies that functional uncoupling of hNav1.7/A1632E dimers rescues the pain-causing molecular phenotype by interferes with an allosteric fast inactivation mechanism, which we link for the first time to channel dimerization. Our work supports the concept of sodium channel dimerization and reveals its relevance to human pain syndromes.

neuroscience↗