Objective/Rationale:
Neurodegeneration has proven notoriously difficult to study. The main barrier to progress has been the challenging, heterogeneous nature of brain tissue. Optogenetics is a neuromodulation method that allows fast and specific bidirectional control of defined brain circuits in intact systems.
Project Description:
We will use technical expertise with optogenetics to test the efficacy of deep brain stimulation and levodopa in a novel optogenetic pre-clinical model where the experimenter has complete control over onset, offset and degree of motor impairment.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If confirmed to respond to currently used therapeutical methods such as deep brain stimulation and levodopa, the optogenetic PD model can facilitate novel therapeutic discovery. Unique features of the model include compatibility with sophisticated cognitive behaviors and neuronal activity recordings not possible or difficult in a less advanced model; tunability (so it recapitulates multiple stages of the disease from mild to advanced in the same subject); and reversibility for acute exposure to light.
Anticipated Outcome:
This model should aid drug screening for Parkinson’s with benefits that include ease-of-use, cost, reliability and reduced use of models.