A Partial Dopamine Lesion Impairs Performance on a Procedural Learning Task: Implications for Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a prevalent neurodegenerative disease which affects the dopamine (DA) cells of the ventral midbrain. Although PD has primarily been thought of as a disorder of the motor system, clinical evidence now shows that subtle neuropsychological abnormalities are present relatively early in the disease process. These deficits are dissociated from Alzheimer-type impairments of short-term memory. Instead PD patients have difficulties learning routines in new circumstances, known as procedural learning. Frontostriatal networks are believed to mediate procedural learning, but little is known about the specific circuitry involved. We used low, chronic doses of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to create a model of early PD. We then tested normal and partially lesioned animals on a simple procedural learning task. All normal animals succeeded on the task on the first trial. Partially lesioned animals naive to the task were unable to solve it over repeated trials. A partially lesioned animal that had solved the task prior to MPTP lesioning retained the strategy, and successfully completed the task on the first trial after MPTP. Behavioral results were correlated with regional changes in staining for tyrosine hydroxylase in the midbrain and striatum.