Some characterization of muscle spindle responses in vitro has been done in the cat, ,, , and rat, , but to our knowledge, there have been no similar studies on mouse muscle spindle afferents. An in vitro muscle-nerve preparation allows for the study of the direct response of a perturbation on the afferents and affords greater pharmacological and ionic control than in vivo preparations, though the ability to study integrated responses is sacrificed. While in vivo preparations provide for studies of spindle function with intact circulatory and spinal circuitry, confounding variables include anesthetic choice, decerebration, and muscle perfusion status. Due to the small size of the mouse, direct recording of afferent cell bodies in the dorsal root ganglia, and intra-axonal recording of afferents have rarely been done in vivo. Skeletal muscle spindle afferent activity has largely been studied using in vivo preparations in the human, ,, ,, cat, ,, ,, , and rat. Many conditions, including chronic muscle pain, , aging, ,, , and diabetes, , involve changes in muscle spindle morphology or afferent activity. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. Hochman served as paid consultant in an RLS advisory board meeting that was organized by Pfizer Inc. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: This work was supported by a grant from Pfizer and S. Hochman and an individual fellowship from the United States National Institutes of Health (K12 GM000680 ) to K. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was supported by a grant from Pfizer (WS753098 ) to S. Received: MaAccepted: Published: June 20, 2012Ĭopyright: © 2012 Wilkinson et al. Overall, spindle afferent response properties were comparable to those seen in other species, supporting subsequent use of the mouse genetic model system for studies on spindle function and dysfunction in an isolated muscle-nerve preparation.Ĭitation: Wilkinson KA, Kloefkorn HE, Hochman S (2012) Characterization of Muscle Spindle Afferents in the Adult Mouse Using an In Vitro Muscle-Nerve Preparation. We conclude that the population of spindle afferents combines to encode stretch in a smoothly graded manner over the physiological range of lengths and speeds tested. These responses and related measures of dynamic sensitivity were not able to categorize units as primary (group Ia) or secondary (group II) even when tested with more extreme length changes (10% Lo). The ramp component of stretch generated dynamic firing responses. Cooling the muscle to 24☌ decreased baseline firing frequency and units correspondingly entrained to slower frequency vibrations. Most units preferentially entrained to vibration frequencies close to their baseline steady-state firing frequencies. As a population, muscle spindle afferents could entrain 1:1 to sinusoidal vibrations throughout the frequency (10–100 Hz) and amplitude ranges tested (5–100 µm). Peak firing frequency increased with ramp speeds (20% Lo/sec, 40% Lo/sec, and 60% Lo/sec). Muscle spindle afferent static firing frequencies increased linearly in response to increasing stretch lengths to accurately encode the magnitude of muscle stretch (tested at 2.5%, 5% and 7.5% of resting length ). Responses were measured at both room (24☌) and muscle body temperature (34☌). We utilized an in vitro adult mouse extensor digitorum longus (EDL) nerve-attached preparation to characterize the responses of muscle spindle afferents to ramp-and-hold stretch and sinusoidal vibratory stimuli.
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