Biology subjects

Almokdad, M.

Publications and source records attributed to Almokdad, M..

4 recordsLinked to original sources

bioRxiv2026

Physiological robustness of MScanFit to simulated motor unit loss and remodelling

Introduction: MScanFit estimates motor unit number and size from compound muscle action potential (CMAP) scans, but its accuracy may depend on the physiological processes that shape motor unit loss and remodelling. We reproduced the general dynamic remodelling framework used in the original MScanFit simulation and expanded it to test MScanFit robustness across physiologically heterogeneous conditions. Methods: Generative computational models simulated CMAP scans from motor unit pools undergoing progressive loss from 160 to 5 surviving motor units. Twelve remodelling conditions combined denervation pattern (random or selective), reinnervation method (random, distributive, or size-weighted), and neuromuscular resilience (20% or 60%); two additional conditions modelled denervation without collateral reinnervation. MScanFit estimates were compared with the known motor unit numbers and mean motor unit sizes used to generate each scan. Results: MScanFit reproduced the principal behaviour reported in the original simulation and generally tracked progressive motor unit loss across heterogeneous remodelling conditions. However, motor unit number estimation (MUNE) error changed systematically with remodelling physiology. Selective denervation and distributive reinnervation increased error at several intermediate stages of motor unit loss, whereas 60% resilience produced greater error than 20% resilience at every stage after remodelling began. Motor unit size estimates also tracked the underlying increase in mean unit size, but their accuracy was more strongly affected by remodelling, particularly with 60% resilience and advanced motor unit loss. Conclusion: MScanFit motor unit number estimates were broadly robust to substantial motor unit loss and neuromuscular remodelling but were not physiologically invariant. Denervation and collateral reinnervation systematically influenced the magnitude and direction of estimation error, indicating that variation in MScanFit performance can arise from differences in the underlying motor unit population. These findings support MScanFit as a robust measure of motor unit loss across heterogeneous neuromuscular phenotypes and show that some of its estimation variability has a physiological basis.

neuroscience↗

bioRxiv2026

Activity-dependent structural plasticity of myelinated axons tunes their excitability

Myelinated axons are classically viewed as stable cables of fixed geometry. We show here that a brief subthreshold stimulation of single nodes in mouse dorsal column axons drives a rapid, lasting structural change: the stimulated axons shrink locally along the internode segments adjacent to the node, to about 70% of their diameter within a few seconds, while neighbouring glia swell to fill the space, sparing the node, paranode and more distant internodes. The thinned axon becomes markedly more excitable for hours, by an amount cable theory predicts from its shorter internodal length constant rather than from active currents that tend to decay over long periods. Using a grease-gap signal that reports the axial-conductance change, we find the axon thinning requires under-myelin Kv1 channels, Na/K-ATPase pumps, bicarbonate, and altered pH, consistent with a regenerative periaxonal potassium build-up that osmotically compresses the axon and swells glia, as previously proposed for physiological high-frequency firing. We present evidence that this mechanism may contribute to the long-lasting clinical benefits of spinal cord stimulation. Axonal GABAA receptor activation reproduces and occludes the plasticity induced by stimulation, indicating that they share a common underlying mechanism. Activity-dependent axon thinning thus enables potent physiologically relevant long term control of conduction, with potential clinical applications.

neuroscience↗

bioRxiv2025

The anterior cingulate cortex drives lateralized age-dependent modulation of claustrum circuits

The anterior cingulate cortex (ACC) sends top-down inputs to the claustrum during sensory, motor, and cognitive processing. This ACC input is thought to drive the activation of claustrum neurons which in turn project back to the cortex to help orchestrate cortical networks during demanding cognitive states such as attention. However, the circuit mechanisms underlying ACC-claustrum signaling are not fully understood. Using in vivo single neuron recordings in mice, we show that ACC neuron activation drives a lateralized modulation of claustrum excitability that changes as a function of postnatal age. In adulthood, ACC activation evoked feed-forward inhibition of ipsilateral excitatory claustrum neurons and activation of contralateral excitatory claustrum neurons. Chemogenetic manipulation in adult mice revealed that ipsilateral claustrum inhibition by the ACC was due to feed-forward activation of claustrum parvalbumin inhibitory neurons. However, in neonatal mice, which lack mature parvalbumin interneurons, ACC inputs evoked claustrum excitation. In juvenile mice, the developmental switch from ACC-evoked claustrum excitation to inhibition occurred in parallel with the maturation of claustrum parvalbumin interneurons, thus corroborating the chemogenetic findings. Therefore, this work provides a novel mechanism of cortical control over claustrum activity that is refined during early postnatal life.

neuroscience↗

bioRxiv2023

A simple and reliable method for claustrum localization across age in mice

1.The anatomical organization of the rodent claustrum remains obscure due to lack of clear borders that distinguish it from neighboring forebrain structures. Defining what constitutes the claustrum is imperative for elucidating its functions. Methods based on gene/protein expression or transgenic mice have been used to spatially outline the claustrum but often report incomplete labeling and/or lack of specificity during certain neurodevelopmental timepoints. To reliably identify claustrum cells in mice, we propose a simple immunolabelling method that juxtaposes the expression pattern of claustrum-enriched and cortical-enriched markers. We determined that claustrum cells immunoreactive for the claustrum-enriched markers Nurr1 and Nr2f2 are devoid of the cortical marker Tle4, which allowed us to differentiate the claustrum from adjoining cortical cells. Using retrograde tracing, we verified that nearly all claustrum projection neurons lack Tle4 but expressed Nurr1/Nr2f2 markers to different degrees. At neonatal stages between 7 and 21 days, claustrum projection neurons were identified by their Nurr1-postive/Tle4-negative expression profile, a time-period when techniques used to localize the claustrum in adult mice are ineffective. Finally, exposure to environmental novelty enhanced the expression of the neuronal activation marker cFos in the claustrum region. Notably, cFos labeling was mainly restricted to Nurr1-positive cells and nearly absent from Tle4-positive cells, thus corroborating previous work reporting novelty-induced claustrum activation. Taken together, this method will aid in studying the claustrum during postnatal development and may improve histological and functional studies where other approaches are not amenable.

neuroscience↗