The Importance of Graft Placement and Task Complexity for Transplant-Induced Recovery of Simple and Complex Sensorimotor Deficits in Dopamine Denervated Rats.
The present study examined the role of graft placement and behavioural task complexity in determining the functional efficacy of intrastriatal grafts of dopamine-rich fetal ventral mesencephalon (VM) placed in the dopamine (DA) depleted striatum. The functional effects of two different striatal placements of VM grafts were evaluated using tests of drug-induced motor asymmetry, simple sensorimotor orienting response, and a more complex sensorimotor integrative task (disengage behaviour), in which the rat has to perform the orienting response while in the act of eating. Rats with complete unilateral 6-hydroxydopamine (6-OHDA) lesions of the mesostriatal DA pathway, received either implants of dissociated fetal VM in the central or ventrolateral portions of the denervated striatum. Nongrafted lesioned rats served as controls. Nine weeks after grafting, the rats were tested on separate days for disengage behaviour, sensorimotor orientation, and amphetamine-induced rotational behaviour. Consistent with previous findings, the two graft placements had differential effects on drug-induced motor asymmetry and sensorimotor responses: the centrally placed VM grafts reversed amphetamine-induced rotational asymmetry but had little effect on the sensorimotor deficit, whereas the ventrolaterally placed grafts reversed the sensorimotor orientation deficits without any effect on the drug-induced rotation. In contrast, fetal VM grafts, regardless of their placement, did not ameliorate the observed deficits in disengage behaviour; that is the grafted rats that had recovered their sensorimotor response in the absence of food were unable to perform the same orienting response while eating. These results provide evidence that functional intrastriatal VM grafts which are capable of restoring sensorimotor responses or motor asymmetry fail to affect lesion-induced deficits in a task that requires more complex sensorimotor integration. It is suggested that the degree of anatomical integration of the grafted DA neurons into the host circuitry will determine the efficacy of the grafts to influence more complex sensorimotor integrative deficits in the DA lesion model.
Mandel
Ronald J.
RJ
Department of Medical Cell Research, Section of Neurobiology, University of Lund, S-223 62 Lund, Sweden.
Brundin
Patrik
P
Björklund
Anders
A