Linking Motoneuron PIC Location to Motor Function in Closed-Loop Motor Unit System Including Afferent Feedback: A Computational Investigation

Abstract

The goal of this study is to investigate how the activation location of persistent inward current (PIC) over motoneuron dendrites is linked to motor output in the closed-loop motor unit. Here, a physiologically realistic model of a motor unit including afferent inputs from muscle spindles was comprehensively analyzed under intracellular stimulation at the soma and synaptic inputs over the dendrites during isometric contractions over a full physiological range of muscle lengths. The motor output of the motor unit model was operationally assessed by evaluating the rate of force development, the degree of force potentiation and the capability of self-sustaining force production. Simulations of the model motor unit demonstrated a tendency for a faster rate of force development, a greater degree of force potentiation, and greater capacity for self-sustaining force production under both somatic and dendritic stimulation of the motoneuron as the PIC channels were positioned farther from the soma along the path of motoneuron dendrites. Interestingly, these effects of PIC activation location on force generation significantly differed among different states of muscle length. The rate of force development and the degree of force potentiation were systematically modulated by the variation of PIC channel location for shorter-thanoptimal muscles but not for optimal and longer-than-optimal muscles. Similarly, the warm-up behavior of the motor unit depended on the interplay between PIC channel location and muscle length variation. These results suggest that the location of PIC activation over motoneuron dendrites may be distinctively reflected in the motor performance during shortening muscle contractions. Keywords: L-type Ca v 1.3 channel, persistent inward current, motoneuron, dendrites, motor unit, muscle length, muscle spindle 3 Significance Statement How may the location of persistent inward current (PIC)-generating Ca v 1.3 channels over spinal motoneuron dendrites affect the force production of the motor unit? To systematically investigate this fundamental issue, a physiologically realistic model of closed-loop motor unit including muscle spindle feedback is built. The computational analysis of model motor unit hierarchically reveals the functional link of the PIC channel location in motoneuron with the input-output properties of closed-loop motor unit under isometric contraction at various muscle lengths. The present study reports that the motor performance during shortening muscle contractions may distinctively reflect the location of PIC activation over motoneuron dendrites. These results would provide useful insights into spinal mechanisms and motor unit function in control of movement.

Tutorial: using NEURON for neuromechanical simulations

“…This section demonstrates the use of pointers by adapting a published neuromuscular model by Kim, which is available on (Kim, 2017 , 2020 ; McDougal et al, 2017 ; Kim and Heckman, 2023 ). To the best of our knowledge, this model is the only published treatment of muscle dynamics that has been implemented entirely in NEURON.…”

“… Overview and output of a neuromuscular model adapted from Kim ( 2020 ). Left : Arrows indicate dependencies between code modules.…”

“…Using the full model, Figure 1 shows the output, including neuron action potentials, calcium concentration, and muscle force. Note that the Kim model (Kim, 2017 , 2020 ), which served as a basis for the model used here, achieved a modular programming design without using pointers. Appendix 1.1 in Supplementary material discusses differences between Kim's implementation and ours.…”