An Explanation for Reflex Blink Hyperexcitability in Parkinson’s Disease. I. Superior Colliculus

Abstract

Hyperexcitable reflex blinks are a cardinal sign of Parkinson's disease. 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, the basal ganglia could modulate the brainstem reflex blink circuits via descending cortical projections. Alternatively, with its inhibitory input to the superior colliculus, the basal ganglia could regulate brainstem reflex blink circuits via tecto-reticular projections. Our study demonstrated that the basal ganglia utilizes its GABAergic input to the superior colliculus to modulate reflex blinks. In rats with previous unilateral 6-hydroxydopamine (6-OHDA) lesions of the dopamine neurons of the SNc, we found that microinjections of bicuculline, a GABA antagonist, into the superior colliculus of both alert and anesthetized rats eliminated the reflex blink hyperexcitability associated with dopamine depletion. In normal, alert rats, decreasing the basal ganglia output 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 that effective muscimol microinjection and microstimulation sites in the superior colliculus overlapped the nigrotectal projection from the basal ganglia. These data support models of Parkinsonian symtomatology that rely on changes in the inhibitory drive from basal ganglia output structures. Moreover, they support a model of Parkinsonian reflex blink hyperexcitability in which the SNr-SC target projection is critical.

Initial clinical manifestations of Parkinson's disease: features and pathophysiological mechanisms

“…For example, a low blinking rate suggests direct inhibition of the central pattern generators, whereas increased excitability of the blink refl ex and Meyerson's sign might be caused by SNr overinhibition of the superior colliculus and secondary disinhibition of the nucleus gigantocellularis. 33 Brainstem mechanisms are also likely to be engaged in the origin of postural disturbances and other motor signs such as dysphagia and dysarthria; however, these features typically occur later in the disease. Bradykinesia can be understood as a failure of neuronal recruitment or "energisation".…”

Role of cerebellum in adaptive modification of reflex blinks.

“…In all mammalian species tested, the OOemg response to the second of two identical stimuli was less than that to the first stimulus for short interstimulus intervals Basso et al 1996;Powers et al 1997). With these paired corneal stimuli, Purkinje cells exhibited a complex spike in response to the first stimulus, but no complex spike or burst of simple spike discharge in response to the second stimulus ( Fig.…”

“…The details of the procedures used in this study have been reported in previous studies (Evinger et al 1993;Basso et al 1996). The animals were prepared for recording electromyograph (EMG) activity of the lid closing, orbicularis oculi muscle (OOemg) and single-unit, extracellular recording.…”

Dystonia Pathophysiology: A Critical Review

“…The increased spontaneous blink rate may result from the increased excitability of the trigeminal system which is dependent on the basal ganglia (83,84). It seems that reduction in dopamine induces a reduction in nucleus raphe magnus activity via the subtantia nigra pars reticulata and superior colliculus (85,86). Schicatano and collegues created a two component model of benign blepharospasm based on the combination of a permissive condition (dopamine depletion) and a precipitating event (corneal irritation and dry eye caused by partial lesion of the zygomatic branch of the facial nerve).…”