Abstract
Post Activation Depression (PActD) is a long lasting depression of Ia afferent EPSPs in response to repetitive activation. This is of clinical relevance given its consistent reduction across a range of spastic disorders. We used in vivo intracellular recording in mice to explore changes in PActD in both normal aging and in the neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS). We used both wild type (WT) C57BL/6J mice and the G127X SOD1 transgenic model of ALS (Jonsson et al 2004)Mice were anaesthetized with Hypnorm (0.315mg/mL fentanyl-citrate +10mg/mL fluanisone), Midazolam (5mg/mL) and water, mixed 1:1:2 (induction: 0.15mL/25g, maintenance: 0.05mL/20min, SC). Anaesthesia was assessed by the lack of reflexes to a short noxious pinch on the hind foot. All mice received Atropine (0.02mg, SC). Prior to recording, mice were ventilated and paralysed with Pancuronium Bromide (0.01mg/h, IP). Anaesthesia was then maintained using the above doses and monitored by heart rate. Intracellular recordings were made with sharp microelectrodes (for detailed methods see Meehan et al 2010). Mean values are given with SD.Motoneurones were antidromically identified by stimulation of the common peroneal or tibial nerves. The stimulation was then reduced to below spike threshold to visualise the monosynaptic EPSP. A 20Hz train of 4 EPSPs was followed by a test EPSP with a varied time delay with respect to the train. Depression was expressed as the size of the test EPSP with respect to the first EPSP of the train. PActD in mice was similar to that observed in larger animals by Hultborn et al. (1996) with respect to both the magnitude and the time course (~79% at the 0.5sec time interval gradually diminishing to 100% by the 4sec interval). The following values are means±SD at the 0.5sec interval.PActD was significantly reduced in aged mice (~580days old) compared to adult (~100-200day old) mice (Adult: 79.12% ±4.993, n= 74 cells, 12 mice. Aged: 83.31% ±7.271, n= 31 cells, 4 mice. Two-tailed T-test P=0.0009).Age-matched WT (~200days) were compared to both pre-symptomatic (PS) G127X mice and symptomatic (S) G127X mice. A significant effect was found (WT mice: 77.57% ±5.312, n = 33 cells, 7 mice. PS G127X: 84.05% ±6.487, n=28 cells, 5 mice. S G127X: 82.71 ±4.624, n=18 cells, 2 mice, Kruskall Wallis, P=0.0002). Dunns Multiple comparisons test revealed significant differences between WT and both PS G127X (P<0.0001) and S G127X (P<0.05) mice but no significant difference between PS and S G127X mice.Our result validate the use of mice models to study PActD and show that it is reduced in both normal aging (without spasticity) and in ALS (a disorder with spasticity) questioning a direct causal role in the development of spasticity.
Where applicable, experiments conform with Society ethical requirements
| Original language | English |
|---|---|
| Title of host publication | Proceedings of The Physiological Society |
| Volume | 31 |
| Place of Publication | Physiology 2014 (London, UK) (2014) |
| Publication date | 2014 |
| Article number | PCA070 |
| ISBN (Electronic) | 1749-6187 |
| Publication status | Published - 2014 |