ReviewThe interhemispheric connections of the striatum: Implications for Parkinson's disease and drug-induced dyskinesias

Parkinson's disease (PD) is characterized by loss of nigrostriatal neurons and depletion of dopamine. This pathological feature leads to alterations to basal ganglia circuitry and subsequent motor disability. Pharmacological dopamine replacement therapy with medications such as levodopa ameliorates the symptoms of PD but can lead to motor complications known as drug-induced dyskinesias. We have recently shown that clinically hemiparkinsonian rhesus monkeys do not develop levodopa-induced dyskinesias despite chronic intermittent exposure and significant unilateral loss of nigrostriatal neurons and dopamine. It is currently unclear what mechanisms prevent the onset of dyskinesias in these animals. Based on our study and results from previous lesioning studies in both the rat and monkey models of PD, we hypothesize that one potential mechanism that may prevent the genesis of dyskinesias in these animals is interhemispheric neuromodulation. Two potential interhemispheric connections that may modulate dyskinesias are the interhemispheric nigrostriatal and corticostriatal pathways. Few investigators have examined the interhemispheric nigrostriatal and corticostriatal connections and the functional role they may play in drug-induced dyskinesias in PD. Therefore, in the following review, we assess the neuroanatomical, electrophysiological and behavioral properties of these interhemispheric connections. Future studies evaluating these interhemispheric striatal pathways and the pathophysiological changes that occur to these pathways in the dyskinetic state are warranted to further develop treatments that prevent or mitigate drug-induced dyskinesias in PD.

► Interhemispheric nigrostriatal and corticostriatal connections are present in the rat, cat and primate as demonstrated by tracer studies. ► There is interhemispheric functional coupling between the nigra and striatum as demonstrated by electrophysiological, neurochemical and behavioral studies. ► We hypothesize that loss of interhemispheric nigrostriatal connections leads to drug-induced dyskinesias in Parkinson's disease.