Chronic electromyograms in treadmill running SOD1 mice reveal early changes in muscle activation.

KEY POINTS: The present study demonstrates that electromyograms (EMGs) obtained during locomotor activity in mice were effective for identification of early physiological markers of amyotrophic lateral sclerosis (ALS). These measures could be used to evaluate therapeutic intervention strategies in animal models of ALS. Several parameters of locomotor activity were shifted early in the disease time course in SOD1G93A mice, especially when the treadmill was inclined, including intermuscular phase, burst skew and amplitude of the locomotor bursts. The results of the present study indicate that early compensatory changes may be taking place within the neural network controlling locomotor activity, including spinal interneurons. Locomotor EMGs could have potential use as a clinical diagnostic tool. ABSTRACT: To improve our understanding of early disease mechanisms and to identify reliable biomarkers of amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, we measured electromyogram (EMG) activity in hind limb muscles of SOD1G93A mice. By contrast to clinical diagnostic measures using EMGs, which are performed on quiescent patients, we monitored activity during treadmill running aiming to detect presymptomatic changes in motor patterning. Chronic EMG electrodes were implanted into vastus lateralis, biceps femoris posterior, lateral gastrocnemius and tibialis anterior in mice from postnatal day 55 to 100 and the results obtained were assessed using linear mixed models. We evaluated differences in parameters related to EMG amplitude (peak and area) and timing (phase and skew, a measure of burst shape) when animals ran on level and inclined treadmills. There were significant changes in both the timing of activity and the amplitude of EMG bursts in SOD1G93A mice. Significant differences between wild-type and SOD1G93A mice were mainly observed when animals locomoted on inclined treadmills. All muscles had significant effects of mutation that were independent of age. These novel results indicate (i) locomotor EMG activity might be an early measure of disease onset; (ii) alterations in locomotor patterning may reflect changes in neuronal drive and compensation at the network level including altered activity of spinal interneurons; and (iii) the increased power output necessary on an inclined treadmill was important in revealing altered activity in SOD1G93A mice.

Motoneuron intrinsic properties, but not their receptive fields, recover in chronic spinal injury.

Proper movement execution relies on precise input processing by spinal motoneurons (MNs). Spinal MNs are activated by limb joint rotations. Typically, their movement-related receptive fields (MRRFs) are sharply focused and joint-specific. After acute spinal transection MRRFs become wide, but their manifestation is not apparent, as intrinsic excitability, primarily resulting from the loss of persistent inward currents (PICs), dramatically decreases. PICs undergo a remarkable recovery with time after injury. Here we investigate whether MRRFs undergo a recovery that parallels that of the PIC. Using the chronic spinal cat in acute terminal decerebrate preparations, we found that MRRFs remain expanded 1 month after spinal transaction, whereas PICs recovered to >80% of their preinjury amplitudes. These recovered PICs substantially amplified the expanded inputs underlying the MRRFs. As a result, we show that single joint rotations lead to the activation of muscles across the entire limb. These results provide a potential mechanism for the propagation of spasms throughout the limb.

Musculotendon adaptations and preservation of spinal reflex pathways following agonist-to-antagonist tendon transfer.

Tendon transfer surgeries are performed to restore lost motor function, but outcomes are variable, particularly those involving agonist-to-antagonist muscles. Here, we evaluated the possibility that lack of proprioceptive feedback reorganization and musculotendon adaptations could influence outcomes. Plantaris-to-tibialis anterior tendon transfer along with resection of the distal third of the tibialis anterior muscle belly was performed in eight cats. Four cats had concurrent transection of the deep peroneal nerve. After 15-20 weeks, intermuscular length and force-dependent sensory feedback were examined between hindlimb muscles, and the integrity of the tendon-to-tendon connection and musculotendon adaptations were evaluated. Three of the transferred tendons tore. A common finding was the formation of new tendinous connections, which often inserted near the original location of insertion on the skeleton (e.g., connections from plantaris toward calcaneus and from tibialis anterior toward first metatarsal). The newly formed tissue connections are expected to compromise the mechanical action of the transferred muscle. We found no evidence of changes in intermuscular reflexes between transferred plantaris muscle and synergists/antagonists whether the tendon-to-tendon connection remained intact or tore, indicating no spinal reflex reorganization. We propose the lack of spinal reflex reorganization could contribute the transferred muscle not adopting the activation patterns of the host muscle. Taken together, these findings suggest that musculotendon plasticity and lack of spinal reflex circuitry reorganization could limit functional outcomes after tendon transfer surgery. Surgical planning and outcomes assessments after tendon transfer surgery should consider potential consequences of the transferred muscle's intermuscular spinal circuit actions.