The Neuron Connection: Modeling Parkinson’s Disease

Stererotaxic surgery in rodents provides a valuable means to produce lesions of particular neuronal pathways, allowing scientists to examine the effects of these lesions on the subsequent behavior of animals post-surgery. A well-known application of this approach is the creation of unilateral dopamine-depleted rats using a stereotaxic injection of the neurotoxin 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNc). This rat model of Parkinson's disease was established several decades ago and can be used as a bioassay to screen for novel anti-Parkinson drugs or as an animal model to study the role of dopamine and other neurotransmitters in the basal ganglia. Several weeks post-lesion 6-OHDA rats exhibit some spontaneous ipsilateral rotational behavior due to release of dopamine on the unlesioned side, yet upon casual observation their motor behavior appears surprisingly normal. However, when unilateral 6-OHDA rats are treated with drugs that release dopamine such as amphetamine (AMPH) or that stimulate dopamine receptors such as apomorphine (APO), 6-OHDA rats exhibit moderate to intense rotational behavior, the direction of which, ipsilateral (AMPH) or contralateral (APO), is dependent on the mechanism of action of the drug administered. While the necessity of stereotaxic surgery to create 6-OHDA rats is clear, many faculty, especially those at smaller institutions, may find it difficult or impossible to use this approach in an undergraduate teaching laboratory due to the prohibitive cost of stereotaxic frames (several thousands of dollars a piece) or the intense supervision required in order to monitor survival surgery in anesthetized rats. Another impediment is class size. For example, I have 16 students in each of two laboratory sections of my Neurobiology course at the University of Massachusetts-Boston. With such a large class, it would be difficult to teach 16 students how to do stereotaxic surgery even though I use this procedure in my own research and I have two stereotaxic frames in my laboratory. However, the applications of this rat model of Parkinson's disease can now be brought into every classroom using a novel web-based computer simulation which was created through a unique interdisciplinary effort between students and faculty at Davidson College. The authors of this web site include undergraduate students from three departments: Mathematics (Rose Feor), Psychology (Nicole Mah), and Physics (Tuti Penev), who worked under the supervision of faculty from Psychology (Julio Ramirez), Mathematics (Donna Molinek), and Instructional Technology (Mur Muchane). This project is one component of a joint effort entitled The …