Diverse and complex muscle spindle afferent firing properties emerge from multiscale muscle mechanics

  1. Kyle P Blum
  2. Kenneth S Campbell
  3. Brian C Horslen
  4. Paul Nardelli
  5. Stephen N Housley
  6. Timothy C Cope
  7. Lena H Ting

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Abstract

Despite decades of research, we lack a mechanistic framework capable of predicting how movement-related signals are transformed into the diversity of muscle spindle afferent firing patterns observed experimentally, particularly in naturalistic behaviors. Here, a biophysical model demonstrates that well-known firing characteristics of mammalian muscle spindle Ia afferents – including movement history dependence, and nonlinear scaling with muscle stretch velocity – emerge from first principles of muscle contractile mechanics. Further, mechanical interactions of the muscle spindle with muscle-tendon dynamics reveal how motor commands to the muscle (alpha drive) versus muscle spindle (gamma drive) can cause highly variable and complex activity during active muscle contraction and muscle stretch that defy simple explanation. Depending on the neuromechanical conditions, the muscle spindle model output appears to ‘encode’ aspects of muscle force, yank, length, stiffness, velocity, and/or acceleration, providing an extendable, multiscale, biophysical framework for understanding and predicting proprioceptive sensory signals in health and disease.

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  1. Version published to 10.7554/elife.55177 on eLife
  2. eLife

    ###This manuscript is in revision at eLife

    The decision letter after peer review, sent to the authors on April 11, 2020, follows.

    Summary

    The muscle spindle is one of the most thoroughly studied sensory receptors in the somatosensory system, yet much is still unknown about how it works. Commendably, the authors have attempted to model the responses of spindle sensory afferents using a biophysical model of intrafusal muscle fibers. The model was shown to mimic experimentally recorded afferent activity in a number of situations. Indeed, it is encouraging to see attention being paid again to the elegant complexities of spindle receptors after years of over-simplification in control models. Nevertheless, there are concerns (detailed in the essential revisions below) about those aspects that were left out.

    Essential Revisions

    1. The assumption that extrafusal muscle force can serve as a proxy for intrafusal fiber force needs to be fully addressed. Indeed, there are well known situations for which an assumed correspondence between extrafusal and intrafusal forces would seem to fail to reproduce experimental results. For example, the classical experimental signature used to identify Ia afferents is a cessation in their discharge during an evoked twitch in the extrafusal muscle fibers. Likewise, the model would seem to fail to reproduce spindle afferent responses during imposed length changes with and without concomitant homonymous extrafusal muscle contractions (e.g. Elek, Prochazka, Hulliger, Vincent. In-series compliance of gastrocnemius muscle in cat step cycle: do spindles signal origin-to-insertion length? J. Physiol., 429, 237-258, 1990). The authors need to include additional simulations of these fundamental experimental phenomena and to fully address the outcome in the Discussion.

    2. The authors suggest that their model provides a unifying biophysical framework for understanding muscle spindle activity, yet there was little attention paid to how intrafusal force or yank is transduced into a receptor potential. Such a unifying framework would need to include mechanisms of transduction by mechanically-gated ion channels. As such, the role that sensory transduction mechanisms play in shaping spindle afferent activity needs to be addressed - either in the model or in the Discussion.

    3. The role that intrinsic properties and associated time-varying conductances (e.g. such as those underlying spike-frequency adaptation) in muscle spindle afferents may play in influencing firing dynamics needs to be addressed in the model or in the Discussion.

    4. There needs to be more clarity in the description of the model and what aspects of the model were original and what aspects were based on previous work, for example, that of Campbell et al. (2014) and MyoSim.

    5. The simulated response (i.e. the driving potential) of the biophysical model depicted in Figure 6A to repeated triangular length changes (without pauses) does not resemble the experimental firing rate data to repeated triangular length changes shown in Figure 2B. In particular, the model exhibits marked abbreviation of the responses to the 2nd and 3rd length changes that are not evident in the experimental data of Figure 2. This disparity between experimental and simulated findings needs to be discussed.

    6. Any general model that aims to account for the activity of spindle afferents during natural activities must account for the well-documented independence among alpha, gamma dynamic and gamma static activation patterns and kinematics, whose different effects on Ia activity have been simulated, measured or inferred in a variety of experiments and integrated into previous models (see Mileusnic et al., 2006). The Discussion should identify which scenarios have not been simulated and which might be problematic for their general thesis.

  3. Version published to 10.1101/858209 on bioRxiv