title: 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 hyper-excitability in which the SNr-SC target projection is critical.
authors.affiliation: Department of Psychology, SUNY Stony Brook 11794, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Basso
authors.forename: A S
authors.initials: AS
authors.lastname: Powers
authors.forename: C
authors.initials: C
authors.lastname: Evinger
mesh_terms: D000818:Animals; D001767:Blinking / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D018755:GABA Agonists / Q000494:pharmacology; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000502:physiology; D013477:Superior Colliculi / Q000502:physiology*
chemical_list: D018755:GABA Agonists; D009118:Muscimol; D016627:Oxidopamine