Recovery of function and basal ganglia [ 14C]2-deoxyglucose uptake after nigrostriatal injury

Abstract

Rats with unilateral 6-hydroxydopamine injections along the mesotelencephalic dopaminergic projection showed a profound impairment in localizing somatosensory stimuli on the contralateral body surface at 3 days postoperatively. Approximately one-half of the affected animals recovered the ability to localize tactile stimuli during 6 weeks postoperatively, whereas the remainder did not. When it occurred, the recovery of sensorimotor function began between the third and fifth day postoperatively and plateaued between days 14 and 21. Unilateral damage to these dopaminergic neurons resulted in hemispheric asymmetries of [ 14C]2-deoxyglucose incorporation at 3 days postoperatively. For structures that normally receive a dopaminergic innervation (e.g., neostriatum, nucleus accumbens septi, olfactory tubercle) the autoradiographic density of the injured side was decreased relative to the intact hemisphere. For structures that receive striatal inputs (globus pallidus, entopeduncular nucleus, substantia nigra pars reticulata), the autoradiographic density was increased on the side of the injury. This pattern of altered [ 14C]2-deoxyglucose incorporation was still present at 6 weeks postoperatively in animals that showed no recovery of somatosensory localization during that time. In contrast, rats that did recover showed no hemispheric asymmetries within the anterior neostriatum, globus pallidus, or substantia nigra pars reticulata at 6 weeks postoperatively, and the time course of normalization of metabolic activity in these structures was similar to that for behavioral restoration. These results directly demonstrate the importance of the neostriatum and particular structures efferent to it in the recovery of sensorimotor functions after striatal dopamine depletion. The types of neuronal plasticity within this basal ganglia circuitry responsible for the normalization of [ 14C]2-deoxyglucose incorporation and behavior are discussed.