Functional reactivation of the deafferented neostriatum by nigral transplants

Abstract

Functional deficits following brain lesions can be due not only to the disruption of conduction in specific input and output pathways passing through the site of injury, but also to the loss of important regulatory systems controlling the functional state of neuronal circuitries in areas distant from the lesion. For example, the behavioural disturbances that result from lesions of the nigrostriatal dopamine (DA) pathways^1–3 can be reversed by administration of dopamine receptor-activating drugs, such as L-dopa or apomorphine^4–6. This suggests that the lesioned dopaminergic system, rather than conveying specific input and output signals, is normally acting on neuronal machineries whose activity levels are set by the activity at the dopaminergic synapses. Thus the neurological deficits resulting from these lesions are due to functional inactivation of otherwise intact neostriatal circuitries. Previous studies have shown that intracerebral transplants of embryonic substantia nigra can compensate for drug-induced^7–9 as well as spontaneous asymmetric motor behaviour¹¹ (expressed as a tendency to move in circles towards the lesioned side), whereas the sensorimotor asymmetry, which is pronounced in rats with a unilateral lesion of the nigrostriatal DA pathway^4,10, was unaffected by thetransplant¹¹. We report here that restoration of striatal dopaminergic neurotransmission by nigral transplants in animals with bilateral, complete lesions of the nigrostriatal DA pathways can reinstate not only certain aspects of spontaneous motor behaviour, but also sensorimotor orientation and sensory attention on the side of the body contralateral to the graft.