Neuropsychological Studies of Mptp-Induced Dopamine

Schneider, Jay

Abstract

Research is proposed which will investigate information processing in the caudate nucleus of cats exposed to the dopaminergic toxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Chronic extracellular single unit recordings from caudate neurons will be used to assess how these cells respond to specific sensory signals (somatosensory, visual, auditory stimulation, electrical stimulation of cortex) under normal circumstances and at various times after exposure to MPTP. MPTP causes damage to the nigrostriatal system in the cat causing a distinct behavioral syndrome characterized by an acute phase (approximately 90% striatal dopamine depletion) consisting of parkinsonian motor signs (akinesia, bradykinesia, """"""""freezing"""""""" during attempted movement) and a reduced responsiveness to external stimulation and subacute and chronic phases in which gross motor behavior approximates normal while sensory responsiveness remains somewhat impaired and substantia nigra pathology is extensive as is the striatal dopamine loss (approximately 70%). The present experiment is designed to examine sensory information processing in the caudate nucleus during the various phases of the MPTP-induced behavioral syndrome to see if disturbances in sensory information processing (during times of sub-maximal and maximal dopamine loss) are apparent irrespective of the appearance of motor symptoms. This is important since many of the cognitive changes associated with basal ganglia disease in humans often appear before motor symptoms (and maximal dopamine loss). These experiments should assess the way in which the caudate nucleus processes afferent signals during varying degrees of dopamine denervation and establish the feasibility of future studies of the behavioral physiology of the MPTP syndrome in the cat.