Optogenetic Stimulation of the Pedunculopontine Nucleus GABAergic and Glutamatergic Neurons with 3D Motion Tracking in Open Field Task

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease that affects millions of people around the world. Methods to alleviate the advanced symptoms of PD and improve the patient’s quality of life are burgeoning areas of research. Extensive research has been done on the cholinergic neurons and their role in alleviating advanced PD symptoms such as freezing of gait and postural control impairment. These research efforts have led to implementation of Deep Brain Stimulation (DBS) in the area as a form of therapy. However, there are three times as many GABAergic neurons and four times as many glutamatergic neurons in the area of interest as there are cholinergic neurons. Despite the population size, there has not been as much investigation into the role of the GABAergic and the glutamatergic neurons of the PPN on movement. The overarching goal of this study is to identify the role of the GABAergic and glutamatergic neurons in the PPN with respect to locomotion using mice models. To do so, optogenetics and 3D motion capture will quantify the effects on movement when the GABAergic and glutamatergic neurons of the PPN are stimulated. This study hypothesizes that stimulation of the GABAergic neurons will result in an inhibition of movement and will effect postural control while that of glutamatergic neurons will increase locomotion velocity. To do so, the study will explore the potential role of the GABAergic and glutamatergic neurons in the pedunculopontine nucleus by quantifying effects of optogenetic stimulation on motor behavior using 3D motion capture. Parameters that were explored in this study include, frequency, laterality of stimulation, time period of stimulation, and number of pulses during stimulation. The study showed that higher frequency and power stimulation of GABAergic neurons will inhibit movement of mice and increasing pulse number would extend the period of inhibition. The study also showed that higher frequency and power stimulation of glutamatergic neurons will increase movement of mice and novel spinning behavior. This study is significant because it quantifies the inhibitory motor role of the GABAergic neurons with novel qualifications in motor behavior as well as novel locomotor behavior of glutamatergic neurons in the PPN. This study can be used to identify the balance and locomotor role of brainstem regions such as the PPN on the behavior of mice. The findings may also demonstrate a need for more efficient DBS therapies that are neuron type specific to better alleviate the Parkinson’s disease side effects.