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The Journal of Neuroscience, August 15, 2001, 21(16):6252-6263

Restorative Plasticity of Dopamine Neuronal Transplants Depends on the Degree of Hemispheric Dominance

Guido Nikkhah, Gero Falkenstein, and Christoph Rosenthal

Neurosurgical Clinic, Nordstadt Hospital, D-30167 Hannover, Germany

The ability of dopaminergic (DA) transplants to restore complex sensorimotor behaviors in experimental Parkinson's disease is dependent on graft survival and reinnervation and is likely to be further modified by complex functional graft-host interactions. Here, we examined the impact of hemispheric dominance and extensive testing regimes on the functional capabilities of DA transplants to restore skilled forelimb movements in rats with unilateral 6-hydroxydopamine lesions. Interestingly, a near complete recovery was observed in DA-grafted animals that did not exhibit a strong hemispheric lateralization for paw use before lesion and implantation surgery, whereas animals with a clear lateralization of paw use and grafted into the contralateral hemisphere exhibited only moderate recovery. Finally, animals grafted ipsilateral to the preferred paw were most resistant to functional improvements in skilled forelimb use. However, the influence of hemispheric dominance on the degree of functional DA graft-induced restoration was specific for skilled forelimb use, whereas no such differences were observed in other tests for motor and sensory functions related to the DA system. Furthermore, functional recovery of DA-grafted animals in skilled forelimb use was significantly promoted by extensive behavioral testing regimes indicative of a "learning how to use" the transplant effect.

These findings indicate the importance of the underlying functional architecture of complex sensorimotor behaviors, such as skilled forelimb use, and the DA neurotransmitter system for the plasticity of DA transplants to promoting a more complete behavioral recovery in experimental, and potentially, also in clinical forms of Parkinson's disease.

Key words: Parkinson's disease; 6-hydroxydopamine; skilled forelimb use; stepping; sensorimotor behavior; nigrostriatal dopamine system; hemispheric lateralization

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21166252-12$05.00/0

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