Frataxin Expression in Sensory Neurons Is Required for Muscle Spindle Function and Proprioception

Friedreich's Ataxia is caused by a reduced expression of the mitochondrial protein frataxin and characterized by impaired proprioception, but it is unknown if muscle spindles are affected. This study analyzed muscle spindle structure and function as well as proprioception in a murine model for Friedreich's Ataxia.

We investigated motor coordination, muscle spindle function, and morphology in mice with a selective loss of frataxin in parvalbumin-expressing neurons (FXN-Pvalb-cKO), including proprioceptive afferents, at 6.5- (early symptomatic stage) and 8.5- (late symptomatic stage) weeks-of-age.

Observer-independent gait analysis of control- and 6.5-week-old FXN-Pvalb-cKO mice revealed no change in muscle strength, motor control, gait, and dexterity. In contrast, 8.5-week-old mutant mice showed severe locomotor ataxia and interlimb coordination deficits, indicated by a reduced stride length and regularity index and an increased base of support and print position. Single-unit electrophysiological recordings of proprioceptive afferents revealed a reduced or absent sensitivity to stretch in 8.5-week-old mutant mice. Muscle spindle capsule and the number of intrafusal fibers as well as their sarcomere structure did not differ significantly between mutant and age-matched control mice. The sensory afferent terminal showed minor signs of degeneration, including fragmentation and formation of varicosities.

These results demonstrate that muscle spindles contribute to the motor coordination deficits observed in FXN-Pvalb-cKO mice and that frataxin expression in sensory neurons is required to maintain proprioceptive acuity and normal muscle spindle function. Our results suggest that the motor coordination deficits in patients with Friedreich's Ataxia might be caused by dysfunctional muscle spindles.