Functional analysis of human intrafusal fiber innervation by human γ-motoneurons

Abstract Investigation of neuromuscular deficits and diseases such as SMA, as well as for next generation prosthetics, utilizing in vitro phenotypic models would benefit from the development of a functional neuromuscular reflex arc. The neuromuscular reflex arc is the system that integrates the proprioceptive information for muscle length and activity (sensory afferent), to modify motoneuron output to achieve graded muscle contraction (actuation efferent). The sensory portion of the arc is composed of proprioceptive sensory neurons and the muscle spindle, which is embedded in the muscle tissue and composed of intrafusal fibers. The gamma motoneurons (γ-MNs) that innervate these fibers regulate the intrafusal fiber’s stretch so that they retain proper tension and sensitivity during muscle contraction or relaxation. This mechanism is in place to maintain the sensitivity of proprioception during dynamic muscle activity and to prevent muscular damage. In this study, a co-culture system was developed for innervation of intrafusal fibers by human γ-MNs and demonstrated by morphological and immunocytochemical analysis, then validated by functional electrophysiological evaluation. This human-based fusimotor model and its incorporation into the reflex arc allows for a more accurate recapitulation of neuromuscular function for applications in disease investigations, drug discovery, prosthetic design and neuropathic pain investigations

Functional analysis of human intrafusal fiber innervation by human γ-motoneurons

Abstract Investigation of neuromuscular deficits and diseases such as SMA, as well as for next generation prosthetics, utilizing in vitro phenotypic models would benefit from the development of a functional neuromuscular reflex arc. The neuromuscular reflex arc is the system that integrates the proprioceptive information for muscle length and activity (sensory afferent), to modify motoneuron output to achieve graded muscle contraction (actuation efferent). The sensory portion of the arc is composed of proprioceptive sensory neurons and the muscle spindle, which is embedded in the muscle tissue and composed of intrafusal fibers. The gamma motoneurons (γ-MNs) that innervate these fibers regulate the intrafusal fiber’s stretch so that they retain proper tension and sensitivity during muscle contraction or relaxation. This mechanism is in place to maintain the sensitivity of proprioception during dynamic muscle activity and to prevent muscular damage. In this study, a co-culture system was developed for innervation of intrafusal fibers by human γ-MNs and demonstrated by morphological and immunocytochemical analysis, then validated by functional electrophysiological evaluation. This human-based fusimotor model and its incorporation into the reflex arc allows for a more accurate recapitulation of neuromuscular function for applications in disease investigations, drug discovery, prosthetic design and neuropathic pain investigations

Data from: Distinct activity-gated pathways mediate attraction and aversion to CO2 in Drosophila

Carbon dioxide is produced by many organic processes, and is a convenient volatile cue for insects searching for blood hosts, flowers, communal nests, fruit, and wildfires. Curiously, although Drosophila melanogaster feed on yeast that produce CO2 and ethanol during fermentation, laboratory experiments suggest that walking flies avoid CO2. Here, we resolve this paradox by showing that both flying and walking Drosophila find CO2 attractive, but only when in an active state associated with foraging. Aversion at low activity levels may be an adaptation to avoid CO2-seeking-parasites, or succumbing to respiratory acidosis in the presence of high concentrations of CO2 that exist in nature. In contrast to CO2, flies are attracted to ethanol in all behavioral states, and invest twice the time searching near ethanol compared to CO2. These behavioral differences reflect the fact that whereas CO2 is generated by many natural processes, ethanol is a unique signature of yeast fermentation. Using genetic tools, we determined that the evolutionarily ancient ionotropic co-receptor IR25a is required for CO2 attraction, and that the receptors necessary for CO2 avoidance are not involved. Our study lays the foundation for future research to determine the neural circuits underlying both state- and odorant- dependent decision making in Drosophila