title: Postactivation depression of the Ia EPSP in motoneurons is reduced in both the G127X SOD1 model of amyotrophic lateral sclerosis and in aged mice.
abstract: Postactivation depression (PActD) of Ia afferent excitatory postsynaptic potentials (EPSPs) in spinal motoneurons results in a long-lasting 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 glutamate-induced 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.
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Panum Institute, Copenhagen, Denmark; and.
authors.forename: A
authors.initials: A
authors.lastname: Hedegaard
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Panum Institute, Copenhagen, Denmark; and.
authors.forename: J
authors.initials: J
authors.lastname: Lehnhoff
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Panum Institute, Copenhagen, Denmark; and.
authors.forename: M
authors.initials: M
authors.lastname: Moldovan
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Panum Institute, Copenhagen, Denmark; and.
authors.forename: L
authors.initials: L
authors.lastname: Grøndahl
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Panum Institute, Copenhagen, Denmark; and Department of Nutrition, Exercise and Sports, University of Copenhagen, Panum Institute, Copenhagen, Denmark.
authors.forename: N C
authors.initials: NC
authors.lastname: Petersen
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Panum Institute, Copenhagen, Denmark; and claire@sund.ku.dk.
authors.forename: C F
authors.initials: CF
authors.lastname: Meehan
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D005260:Female; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008839:Microelectrodes; D009046:Motor Neurons / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
chemical_list: C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1
keywords: ALS; aging; postactivation depression