,~l~uro,~eien~e Vol. 9, No. 4, pp. 879-888, 1983 Printed in Great Rritain 0306-4522~83 $3.00 + 0.00 Pergamon Press Ltd 1BRO BEHAVIORAL AND N~URONAL REORGANIZATION AFTER UNILATERAL SUBSTANTIA NIGRA LESIONS: EVIDENCE FOR INCREASED INTERHEMISPHERIC NIGROSTRIATAL PROJECTIONS M. PRITZEL, J. P. HUSTON and M. SARTER institute of Psychology III, University of Dijsseldorf, Universitltsstrasse 1 D-4000 Diisseldorf, F.R.G. Abstract----This study was intended to investigate the possibility of a relationship between compensation of sensory-motor asymmetries induced by unilateral substantia nigra lesions and changes in inter- hemispheric ni~ost~atal projections. Adult male rats were used in two experiments: Experiment I. Animals received an injection of either ~OH~opamine or kainic acid into the substantia nigra. They were observed for intervals of 7, 21 or 90 days with respect to spontaneous turning, d-amphetamine-induced turning and other sensory-motor asymmetries. Interhemispheric nigrostriatal projections were examined by injecting horseradish peroxidase into the striatum homolateral to the nigral lesion. Labeled perikarya were counted in the contralateral substantia nigra. A significant increase in number of labeled neurons was observed 7 and 21 days, but not 90 days after the nigral lesion in comparison to control animals. Spontaneous lesion-induced turning behavior ceased within the first postopemtive week. After 21 and 90 days it was still possible to elicit turning by injection of amphetamine. Experiment II. An increase in number of interhemispheric nigro striatal projections one week after the nigrai lesion was also found when Nuclear Yellow was used as a tracer substance. Animals received a unilateral injection of Fast Blue into the caudate nucleus, followed by an injection of Nuclear Yellow at the identical locus one week later. An increase in number of Nuclear Yellow-labeled neurons was registered only if the injection of Fast Blue was followed by a 6-hydroxydopamine lesion in the homolaterat substantia nigra within 24 h. Interhemispheric nigro striatal projections were of mono- aminergic as well as of non-monoaminergic origin, as revealed by histofluorescent tracing for mono- aminergic neurons. These results may reflect sprouting of interhemispheric fiber projections in response to, or as correlates of. behavioral compensation of the lesion-induced behavioral asymmetries. Recently, we surgically ablated the tclencephalon on one side of the brain and injected the tracer horse- radish peroxidase (HRP) unilaterally into the thal- amus either ipsilateral or contralateral to the side of the ablation. When injected into the ipsilateral thal- amus, we found many HRP-labeled cells in sites in the contralateral part of the brain which in the intact animals project to the contralateral thalamus sparsely or not at a11.25~29 For example, after injection of HRP into the ventral medial thalamus of the damaged but not the intact hemisphere, labeled cells were found in the contralateral substantia nigra (SN). The appear- ance of labeled cells appeared as early as one week after the lesion when spontaneous circling behavior bad ceased. Similar results were obtained with uni- lateral 6-hydroxydopamine (BOHDA) or kainic acid (KA) lesions of the substantia nigra.30 In these pre- parations HRP-labeled cells were found in the SN in the intact side of the brain after injection of HRP into the ventral medial thalamus of the contralateral hemisphere 7 days after the operation, when sponta- zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJI Abbreviations: HRP, horseradish peroxidase; KA, kainic acid; 6-OHDA, 6-hydroxydopamine; SN, substantia nigra. neous turning behavior induced by the 6-OHDA lesion’ had ceased. The increase in number of labeled cells in contralateral projection sites may have been the result of terminal sprouting of crossed projections after ipsilateral denervation. Reactive synaptogenesis of crossed projections in the CNS after interruption of the ipsilateral innervation, and uice versa, has been reported in a number of instances.‘~4~‘0~‘4~22~z3~33~4’~~ An example of homotypical reactive synaptogenesis oc- curs after unilateral destruction of the entorhinal cortex.38,39,40 In this case the lost innervation of the ipsilateral dentate gyrus is replaced by sprouting of homologous fibers from the contralateral entorhinal cortex.39”0 Our results may reflect such a process of replace- ment of ipsilaterally deafferented synapses with sprouting of sparse homotypical crossed projections. One of the prerequisites for this interpretation, namely the presence of a sparsely developed inter- hemispheric nigrothalamic projection in the intact rat, which may then sprout in response to ipsilateral deafferentation, was confirmed only recently by Gerfen et al.” The rough temporal relationship between the ap- 879