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Plasticity in Spinal Networks: Injury and Rehabilitation

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  • Full or part time
    Dr R M Ichiyama
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

We have previously demonstrated that in these chronic stages of SCI, months after the initial insult, the spinal cord caudal to the lesion changes substantially. Cats that received a complete mid-thoracic transection had elevated levels of glutamate decarboxylase (GAD65 and 67), a GABA synthetic enzyme, in segments caudal to the lesion 3 to 12 months after the lesion (Tillakaratne et al., 2000), whichcorrelates with persistent impairments in behaviour. We have also reported that in neonatally (P5) transected (midthoracic) rats, motoneurons develop greater afterhyperpolarization depth and significantly smaller central and segmental excitatory post synaptic potentials (epsps) 2-3 months after lesion (Petruska et al., 2007). These results strongly suggest that in the chronic stages of an SCI, the environment caudal to the lesion becomes inhibitory to motoneuron firing, and consequently detrimental to muscle activation and behaviour.
Locomotor training has been one of the most successful strategies to improve functional recovery in chronic stages of spinal cord injury (SCI) both experimentally and clinically (Edgerton et al., 2008). Step or stand training in cats (Lovely et al., 1986; Barbeau and Rossignol, 1987; Lovely et al., 1990; De Leon et al., 1998; Tillakaratne et al., 2002; Boyce et al., 2007) results in significant behavioural improvements, accompanied by significant decreases in GAD67 expression (Tillakaratne et al., 2002). We have also demonstrated that in rats transected as neonates (P5), locomotor training resulted in significant facilitation of motoneuron epsps and decreases in afterhyperpolarisation (AHP) depth (Petruska et al., 2007), similar to non-injured controls. These results suggest that locomotor training actively changes the synaptic composition of motoneurons in the absence of supraspinal fibres regrowth.
In vivo techniques in combination with cellular, molecular and pharmacological techniques will be used to investigate the underlying neurophysiological mechanisms associated with the behavioural recovery.

Funding Notes


Journal of Neuroscience (2011), 31(1): 26-33.
Locomotor Training Maintains Normal Inhibitory Influence on Both Alpha- and Gamma-Motoneurons after Neonatal Spinal Cord Transection
R. M. Ichiyama, J. Broman, R.R. Roy, H. Zhong, V. R. Edgerton & L.A. Havton

Brain Research Bulletin (2011), 84(4-5): 327-336.
Movement Rehabilitation after Spinal Cord Injuries: Emerging Concepts and Future Directtions
B. C. Marsh, S.L. Astill, A. Utley & R.M.Ichiyama

Respiratory Physiology & Neurobiology (2010), 174: 76-88.
The role of serotonin in respiratory function and dysfunction.
G.Hilaire, N. Voituron, C. Menuet, R.M.Ichiyama, H.H. Subramanian & M. Dutschmann.

Nature Neuroscience (2009), 12(10): 1333-1342.
Transformation of nonfunctional spinal circuits into functional states after the loss of brain input.
G. Courtine, Y. Gerasimenko, R. van den Brand, A. Yew, P. Musienko, H. Zhong, B. Song, Y. Ao, R.M. Ichiyama, I. Lavrov, R.R. Roy, M.V. Sofroniew & V.R. Edgerton

PLoS One (2009), 4(8):e6862.
Enhanced motor function by training in spinal cord contused rats following radiation therapy.
R. Ichiyama, M. Potuzak, M. Balak, N. Kalderon & V.R. Edgerton.

Brain (2009), 132:1426-40
Differential effects of anti-Nogo –A antibody treatment and treadmill training in rats with incomplete spinal cord injury.
I.C. Maier*, R.M.Ichiyama*, G. Courtine*, L. Schnell, I. Lavrov, V.R. Edgerton & M.E. Schwab
*these authors contributed equally

Journal of Neuroscience (2008), 28(29):7370-7375
Step Training Reinforces Specific Spinal Locomotor Circuitry in Adult Spinal Rats.
R.M. Ichiyama, G. Courtine, Yu. P. Gerasimenko, G. J. Yang, R. van den Brand, I.A. Lavrov, H. Zhong, R.R. Roy &V.R. Edgerton.

Neuroscience Letters (2008), 438 (3): 281-285
Dose Dependence of the 5-HT Agonist Quipazine in Facilitating Spinal Stepping in the Rat with Epidural Stimulation.
R.M. Ichiyama, Y,P. Gerasimenko, D.L. Jindrich, H. Zhong, R.R. Roy & V.R. Edgerton (2008).

How good is research at University of Leeds in Biological Sciences?

FTE Category A staff submitted: 60.90

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