Investigating learning deficits in MPTP monkey models of Parkinson’s disease using a cage-based training system

Background and Aim : Parkinson’s Disease (PD), is a progressive neurodegenerative disorder affecting more than 1% of the population above 60 years of age. Patients with PD suffer from a range of motor difficulties coupled with cognitive deficits. A reliable Non-Human Primate model of PD can help us in finding the neural mechanisms of these deficits. MPTP monkey model of PD, as the most dominant model, can reliably reproduce motor symptoms of PD. However, the reliability of this model in terms of cognitive deficits is not well-studied with a systematic method. In this study, we aim to characterize learning deficiencies in MPTP monkey models of PD using a cage-based training system where monkeys are not forced to do the required task in physically restrained conditions and in a specific time duration predetermined by the experimenter.Methods : In order to invasively engage monkeys with PD in our experiments, we designed a cage-based training system, in which the stimuli were presented on a touch-screen monitor, easily accessible to them. In this method, monkeys are free in their cages and are not under any physical pressure for doing the task. Next, we designed three experiments: a) guided-touch task with variable stimulus size, in which the stimulus size gets smaller over the block of trials, as the monkey’s touch accuracy reaches 85% correct, b) guided-touch with constant stimulus size, in which the stimulus size remains constant over the block of trials, however the position of the stimulus is randomly changing between two locations, and c) two-armed bandit task, in which two stimuli are simultaneously presented on the screen. Choosing one stimulus is always followed by receiving a certain amount of reward, while the other stimulus is not associated with a reward. Monkeys were trained to report their decision by touching the stimulus presented on the screen. In return for each correct response, a certain amount of liquid reward was delivered via an auto-delivery reward system.Results : Our cage-based training system was successful in motivating monkeys to freely engage in doing the tasks. Although slowly, MPTP models of PD could reach an acceptable range of accuracy in the first two experiments, where there was only one target presented on the screen. However, they were unable to achieve accuracy significantly above chance in the third experiment where they had to choose between the two alternatives.Conclusion : We showed that in a two-armed bandit task, MPTP models of PD are not capable of being as accurate as they are in a one-target task, in spite of having the same amount of training. These results do not necessarily suggest the inability of MPTP models of PD in performing two-armed bandit tasks since further investigation is required to show whether extensive training can affect the learning procedure in these tasks. In addition, we believe that our suggested cage-based training system is a reliable method to study the cognitive abilities of MPTP models because of their freedom in deciding to engage in the task.

کلیدواژه ها:

Parkinson s Disease ، Reinforcement Learning ، MPTP monkey models of PD ، Cage-based training