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

TY - JOUR

T1 - Postactivation depression of the Ia EPSP in motoneurons is reduced in both the G127X SOD1 model of amyotrophic lateral sclerosis and in aged mice

AU - Hedegaard, Anne

AU - Lehnhoff, Janna

AU - Moldovan, Mihai

AU - Grøndahl, Lillian

AU - Petersen, Nicolas Caesar

AU - Meehan, Claire Francesca

N1 - CURIS 2015 NEXS 316

PY - 2015/6/18

Y1 - 2015/6/18

N2 - Postactivation depression (PActD) of Ia afferent excitatory postsynaptic potentials (EPSPs) in spinal motoneurons results in a longlasting depression of the stretch reflex. This phenomenon (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 old) C57BL/6J mice is both qualitatively and quantitatively similar to that which has been observed in larger animals with respect to both the magnitude (with ~20% depression of EPSPs at 0.5 ms after a train of stimuli) and the 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 such excitatory inputs to spinal motoneurons may have important implications for hyperreflexia and/or glutamateinduced excitotoxicity in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). With the use of 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 presymptomatic (16% depression) and symptomatic (17.3% depression) time points compared with aged-matched controls (22.4% depression). The PActD reduction was not markedly altered by symptom onset. Comparing these PActD 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 accounted that in aged (580 day old) C57BL/6J mice there was also a reduction in PActD although, aging is not usually associated with spasticity.

AB - Postactivation depression (PActD) of Ia afferent excitatory postsynaptic potentials (EPSPs) in spinal motoneurons results in a longlasting depression of the stretch reflex. This phenomenon (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 old) C57BL/6J mice is both qualitatively and quantitatively similar to that which has been observed in larger animals with respect to both the magnitude (with ~20% depression of EPSPs at 0.5 ms after a train of stimuli) and the 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 such excitatory inputs to spinal motoneurons may have important implications for hyperreflexia and/or glutamateinduced excitotoxicity in the neurodegenerative disease amyotrophic lateral sclerosis (ALS). With the use of 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 presymptomatic (16% depression) and symptomatic (17.3% depression) time points compared with aged-matched controls (22.4% depression). The PActD reduction was not markedly altered by symptom onset. Comparing these PActD 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 accounted that in aged (580 day old) C57BL/6J mice there was also a reduction in PActD although, aging is not usually associated with spasticity.

U2 - 10.1152/jn.00745.2014

DO - 10.1152/jn.00745.2014

M3 - Journal article

C2 - 26084911

SN - 0022-3077

VL - 114

SP - 1196

EP - 1210

JO - Journal of Neurophysiology

JF - Journal of Neurophysiology

IS - 2

ER -