AN EXPLANATION FOR REFLEX BLINK HYPEREXCITABILITY IN PARKINSONS-DISEASE .1. SUPERIOR COLLICULUS

Hyperexcitable reflex blinks are a cardinal sign of Parkinson's diseas e. We investigated the neural circuit through which a loss of dopamine in the substantia nigra pars compacta (SNc) leads to increased reflex blink excitability. Through its inhibitory inputs to the thalamus, th e basal ganglia could modulate the brainstem reflex blink circuits via descending cortical projections, Alternatively, with its inhibitory i nput to the superior colliculus, the basal ganglia could regulate brai nstem reflex blink circuits via tecto-reticular projections, Our study demonstrated that the basal ganglia utilizes its GABAergic input to t he superior colliculus to modulate reflex blinks. In rats with previou s unilateral 6-hydroxydopamine (6-OHDA) lesions of the dopamine neuron s of the SNc, we found that microinjections of bicuculline, a GABA ant agonist, into the superior colliculus of both alert and anesthetized r ats eliminated the refer blink hyperexcitability associated with dopam ine depletion, In normal, alert rats, decreasing the basal ganglia out put to the superior colliculus by injecting muscimol, a GABA agonist, into the substantia nigra pars reticulata (SNr) markedly reduced blink amplitude. Finally, brief trains of microstimulation to the superior colliculus reduced blink amplitude, Histological analysis revealed tha t effective muscimol microinjection and microstimulation sites in the superior colliculus overlapped the nigrotectal projection from the bas al ganglia. These data support models of Parkinsonian symtomatology th at rely on changes in the inhibitory drive from basal ganglia output s tructures. Moreover, they support a model of Parkinsonian reflex blink hyperexcitability in which the SNr-SC target projection is critical.