Postactivation depression of the Ia EPSP in motoneurons is reduced in both the G127X SOD1 model of amyotrophic lateral sclerosis and in aged mice

Post Activation Depression (PActD) of Ia afferent EPSPs in spinal motoneurons results in a long lasting depression of the stretch reflex. PActD is of clinical interest as it has been shown to be reduced in a number of spastic disorders. Using in vivo intracellular recordings of Ia EPSPs in adult mice, we demonstrate that PActD in adult (100-220 days) C57BL/6J mice is both qualitatively and quantitatively similar to that which has been observed in larger animals with respect to both magnitude (approximately 20% depression of EPSPs at 0.5 ms after a stimuli train) and time course (returning to almost normal amplitudes by 5 ms after the train). This validates the use of mouse models to study PActD. Changes in excitatory inputs to spinal motoneurons may have important implications for hyper-reflexia and/or glutamate induced excitotoxicity in the neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS). Using the G127X SOD1 mutant mouse, an ALS model with a prolonged asymptomatic phase and fulminant symptom onset, we observed that PActD is significantly reduced at both pre-symptomatic (16% depression) and symptomatic (17.3% depression) time points compared to aged-matched controls (22.4% depression). Comparing these changes at the EPSP with the known effect of the depression on the monosynaptic reflex, we conclude that this is likely to have a much larger effect on the reflex itself (a 20-40% difference). Nevertheless, it should also be noted that in aged (580 days) C57BL/6J mice there was also a reduction in PActD although, aging is not usually associated with a hyper-reflexia.