Reinnervation of the denervated striatum by substantia nigra transplants: functional consequences as revealed by pharmacological and sensorimotor testing.

Embryonic substantia nigra (SN) was transplanted to the neostriatum in adult rats subjected to a unilateral or serial bilateral destruction of the nigrostriatal dopamine (DA) pathway. The survival of the graft and the growth of DA-containing fibers from the graft into the host brain was studied by fluorescence histochemistry and micro-fluorometry. The motor asymmetry, and the contralateral 'sensory neglect' induced by a unilateral destruction of the nigrostriatal DA pathway, were monitored in the transplanted rats and in non-transplanted controls through repeated measurements of the amphetamine-and apomorphine-induced rotational behaviour, and through analysis of the rats performance in a number of sensorimotor tests. Finally, the development of aphagia and adipsia after a serial bilateral destruction of both nigrostriatal DA pathways were followed in rats bearing bilateral SN transplants and in lesioned non-transplanted controls. The results show that large parts of the dorsal neostriatum can be reinnervated by DA-containing axons from the intracortical transplant and that this new DA input can fully compensate for the amphetamine-induced motor assymmetry that resulted from the initial destruction of the innate nigrostriatal DA pathway. The fluorescence microscopical observations provide strong evidence that the compensation of the amphetamine-induced rotational response was specifically related to the re-establishment of a new DA input to the denervated neostriatum, and that the degree of rotational compensation was well correlated to the magnitude of ingrowth into the neostriatum. Subsequent surgical removal of the SN transplant reinstated the initial rotational behaviour. In sharp contrast to the marked compensation in motor asymmetry, the transplanted rats showed no tendency to recover in their sensorimotor performance. Thus, while the sensorimotor deficit had recovered in the control group a marked contralateral 'sensory neglect' remained in the transplanted animals. Furthermore, removal of the transplant produced a significant improvement in their sensorimotor performance within 3 days. In the bilaterally transplanted animals the presence of the transplants did not prevent the development of severe adipsia, aphagia and akinesia following the destruction of the remaining contralateral nigrostriatal pathway. In fact, the recovery from the consummatory deficits tended to be better in the lesioned control rats than in the transplanted ones. It is concluded that SN transplants reinnervation the dorsal part of the neostriatum are able to replace the innate SN in normalizing some aspects of the rats motor behaviour, while their sensorimotor deficits and deficits in consummatory behaviour were unaffected. It is suggested that this dissociation of transplant-induced recovery is due to the failure of the SN transplants to reinnervate those parts of the neostriatum which are most directly implicated in sensorimotor and consummatory behaviour.