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

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1152/jn.00745.2014

DO - 10.1152/jn.00745.2014

M3 - Journal article

C2 - 26084911

VL - 114

SP - 1196

EP - 1210

JO - Journal of Neurophysiology

JF - Journal of Neurophysiology

SN - 0022-3077

IS - 2

ER -