Knorz, A. L. | Search bioRxiv

bioRxiv2024

The effects of varying intensities of unilateral handgrip fatigue on bilateral movement

The human ability to maintain adequate movement quality despite muscle fatigue is of critical importance to master physically demanding activities of daily life and for retaining independence following motor impairments. Many real-life situations call for asymmetrical activation of extremity muscles leading to unilateral manifestations of muscle fatigue. Repeated unilateral handgrip contractions at submaximal force have been shown to be associated with neural dynamics in both contralateral and ipsilateral cortical motor areas and improved response times of the contralateral, unfatigued homologue in a button-press task. However, it remains unclear whether the observed improvement in contralateral response latency translates into higher-level benefits in movement quality. To investigate this, 30 healthy participants underwent unilateral handgrip fatiguing tasks at 5%, 50%, and 75% of maximum voluntary contraction (MVC) force. Subsequently, bimanual movement quality was assessed in an object-hit task using a Kinarm robot. The protocol at 50% and 75% of MVC elicited clear signs of muscle fatigue compared to the control condition (5%) measured by a decline in force, post-exercise deterioration in MVC, characteristic changes in surface electromyography magnitudes, and increases in ratings of perceived exertion. No change was observed on kinematic measures in the object-hit task for both arms indicating that unilateral handgrip fatigue did not elicit measurable effects on higher-level movement quality on the ipsilateral or contralateral homologue. Previously reported improvements on contralateral response latency were not found to translate into advanced movement quality benefits.

neuroscience↗

bioRxiv2023

Genetic identification of novel medullary neurons underlying congenital central hypoventilation syndrome

Congenital Central Hypoventilation Syndrome (CCHS) is a rare, but life-threatening, respiratory disorder that is classically diagnosed in children. This disease is characterized by pronounced alveolar hypoventilation and diminished chemoreflexes, particularly to abnormally high levels of arterial pCO2. Mutations in the transcription factors PHOX2B and LBX1 have been identified in CCHS patients, but the dysfunctional circuit responsible for this disease remains unknown. Here, we show that distinct sets of medullary neurons co-expressing both transcription factors (dB2 neurons) account for specific respiratory functions and phenotypes seen in CCHS. By combining murine intersectional chemogenetics, intersectional labeling, and the selective targeting of the CCHS disease-causing Lbx1FS mutation to specific subgroups of dB2 neurons, we uncovered novel sets of these cells key for i) respiratory tidal volumes and the hypercarbic reflex, ii) neonatal respiratory stability and iii) neonatal survival. These data provide functional evidence for the essential role of dB2 neurons in neonatal respiratory physiology and will be instrumental for the development of therapeutic strategies for the management of CCHS. In summary, our work uncovers new neural components of the central circuit regulating breathing and establishes dB2 neuron dysfunction to be causative of CCHS.

neuroscience↗