Critique on Hayes et al. paper

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Name: Guoliang (Josh) Zheng
Student ID: 1809910

Hayes HB, Chang YH, Hochman S (2012) Stance-phase force on the opposite limb indicates swing-phase afferent presynaptic inhibition during locomotion. J Neurophysiology 107: 3168-3180

Accurate movement depends on precise activation of multiple muscle groups in a certain pattern. Motor pattern is primarily generated by central neural circuits and spinal reflex activation (Brown, 1914). Phasic sensory signals serve to modulate the central pattern generator to modify motor output (Grillner and Wallén, 2004). During locomotion, sensory input induces presynaptic inhibition (PSI) at afferent terminals in a behaviorally dependent manner to minimize self-induced sensory interference on motor output (Seki et al., 2003). PSI is often characterized by primary afferent depolarization (PAD) mediated by GABAA receptor, and can be measured as dorsal root potential (DRP) (Rudomin and Schmidt, 1999). The pattern of PSI becomes significantly important in interpreting the relationship of sensory feedback and motor consequences, yet only the ipsilateral (I) PSI has been studied extensively despite the literature indicating that contralateral (C) effects might be equally significant (Hayes et al., 2012). In this study, Hayes et al. characterize the pattern of C PSI and hypothesize that the C force and movement will affect the I PSI, and hence gates the sensory input to the spinal cord to minimize influence on motor output.
In this study, the authors use a novel technique dorsal-up spinal cord hindlimb preparation (SCHP) to stably isolate the spinal cord with hindlimbs intact. Electrodes are placed on the 2nd and 5th segment of the lumbar spine dorsal root (L2, L5 DR) to record DRP readings during non-fictive locomotion and the ventral root (VR) of L2 to measure the activity of motor output. NMDA, 5-HT, and DA are used to induce movement of rat models and force platforms are connected to Wheatstone bridge circuitry to amplify the force strength signal. Bicuculline, a GABAA receptor antagonist, is administered to determine whether DRP is GABAA-receptor dependent. Decreased DRP after Bicuculline injection comparing to the normal state indicates DRP generation is GABAA-receptor dependent, and can be used for the study of PAD- mediated PSI pattern. Different timing and magnitude of C limb loading is used to determine whether C force affects the pattern of DRP, and the periodic absence of limb force induced by dopamine is used as a negative control. Figure 2 shows that IL2 DRP scales with C force, but the absence of C force nearly abolishes IL2 DRP. In addition, IL2 DRP remains largely unaffected by the variations of I force. To examine the necessity of limb force on DRP generation, force plate is removed individually to determine if the absence of each limb force affects the pattern of DRP. The data show the dropping of C force nearly abolishes IL2 DRP (n=7/8), yet DRP generation resumes when C force is reapplied, which serves as a positive control. The dropping of I force, on the other hand, has nearly no effect on IL2 DRP (n=6/7). These data not only support the hypothesis that C force and movement affect I DRP pattern, but also indicate C force, not movement, is necessary for the generation of DRP by showing that DRP reduced without force while movement remains.
Statistical analyses are needed to further validate these findings about the spatiotemporal relationship between the pattern of DRP and limb force as well as movement. Significant Pearson Correlation Coefficient (R=0.77, 0.83), computed from the plot of IL2 DRP area and peak against C force area and peak, indicates a strong positive correlation between IL2 DRP and C force, whereas the R (0.04, 0.03) of the plot of IL2 DRP against I force shows relatively weak correlation. Additionally, statistical parameters like concentration (r) and angular dispersion are computed to interpret the
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