Altered Motoneuron Properties Contribute to Motor Deficits in a Rabbit Hypoxia-Ischemia Model of Cerebral Palsy

Cerebral palsy (CP) is caused by a variety of factors attributed to early brain damage, resulting in permanently impaired motor control, marked by weakness and muscle stiffness. To find out if altered physiology of spinal motoneurons (MNs) could contribute to movement deficits, we performed whole-cell patch-clamp in neonatal rabbit spinal cord slices after developmental injury at 79% gestation. After preterm hypoxia-ischemia (HI), rabbits are born with motor deficits consistent with a spastic phenotype including hypertonia and hyperreflexia. There is a range in severity, thus kits are classified as severely affected, mildly affected, or unaffected based on modified Ashworth scores and other behavioral tests. At postnatal day (P)0–5, we recorded electrophysiological parameters of 40 MNs in transverse spinal cord slices using whole-cell patch-clamp. We found significant differences between groups (severe, mild, unaffected and sham control MNs). Severe HI MNs showed more sustained firing patterns, depolarized resting membrane potential, and fired action potentials at a higher frequency. These properties could contribute to muscle stiffness, a hallmark of spastic CP. Interestingly altered persistent inward currents (PICs) and morphology in severe HI MNs would dampen excitability (depolarized PIC onset and increased dendritic length). In summary, changes we observed in spinal MN physiology likely contribute to the severity of the phenotype, and therapeutic strategies for CP could target the excitability of spinal MNs

Estimation of self-sustained activity produced by persistent inward currents using firing rate profiles of multiple motor units in humans

Persistent inward calcium and sodium currents (IP) activated during motoneuron recruitment help synaptic inputs maintain self-sustained firing until de-recruitment. Here, we estimate the contribution of the IP to self-sustained firing in human motoneurons of varying recruitment threshold by measuring the difference in synaptic input needed to maintain minimal firing once the IP is fully activated compared with the larger synaptic input required to initiate firing prior to full IP activation. Synaptic input to ≈20 dorsiflexor motoneurons simultaneously recorded during ramp contractions was estimated from firing profiles of motor units decomposed from high-density surface-EMG. To avoid errors introduced when using high-threshold units firing in their nonlinear range, we developed methods where the lowest-threshold units firing linearly with force were used to construct a composite (control) firing rate profile to estimate synaptic input to the higher-threshold (test) units. The difference in the composite firing rate (synaptic input) at the time of test unit recruitment and de-recruitment (ΔF=Frecruit-Fde-recruit) was used to measure IP amplitude that sustained firing. Test units with recruitment thresholds 1-30% of maximum had similar ΔFs, which likely included both slow and fast motor units activated by small and large motoneurons, respectively. This suggests that the portion of the IP that sustains firing is similar across a wide range of motoneuron sizes. Higher-threshold units had more prolonged accelerations in firing rate at the onset of recruitment compared to lower-threshold units, likely reflecting IP activation closer to firing onset in the higher-threshold units, but well before firing onset in the lower-threshold units

The role of intrinsic muscle mechanics in the neuromuscular control of stable running in the guinea fowl

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66308/1/jphysiol.2009.171017.pd