How Optogenetics Can Help Improve Deep Brain Stimulation for the Motor Symptoms of Parkinson's Disease (P7.043)

OBJECTIVE: The application of optogenetic methods to current deep brain stimulation (DBS) based treatments for Parkinson’s disease (PD). BACKGROUND: Subthalamic DBS is an established treatment option for advancing PD but little is known about its method of action. This lack of knowledge limits refinements of this treatment but new techniques in neuroscience and genetics are allowing us to develop our understanding and improve patient care. Subthalamic DBS is far from perfect, helping only a limited aspect of the symptoms of PD. There is strong evidence which shows that DBS electrode positioning has a profound effect on outcome and that functional limitations exist with current methods. Optogenetics is a growing field that has attempted to tackle some of these issues. Here, relevant data is presented and compared to assess potential changes that can be made to current DBS methods in order to improve patient outcome. DESIGN/METHODS: A systematic review was conducted of papers reporting in vivo studies using optogenetic techniques to interrogate basal ganglia neural circuits. We report data on improvements in motor function, the pathways tested and reliability / reproducibility of the methods. RESULTS: Optical stimulation of striatal “direct” pathway medium spiny projection neurons, primary motor cortex projecting neurons and afferent pathways to the subthalamic nucleus (STN) improve parkinsonian motor symptoms in experimental rodents. CONCLUSIONS: Extrapolating from these results, the most promising DBS target would appear to be the afferent pathways to the STN. This study provides a novel interpretation of existing data that could be directly applied to current treatment methods in the near future and raises hope for a potential role for optogenetics as a treatment in its own right.