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.
Type
Honors thesisDepartment
Psychology and NeurosciencePermalink
https://hdl.handle.net/10161/16715Citation
John, Albin (2018). Optogenetic Stimulation of the Pedunculopontine Nucleus GABAergic and Glutamatergic
Neurons with 3D Motion Tracking in Open Field Task. Honors thesis, Duke University. Retrieved from https://hdl.handle.net/10161/16715.Collections
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