The outer mantle of the brain, the cerebral cortex, plays a significant role in selecting and controlling movements. Changes in the activity of cortical neurons are key to disorders of movement, especially Parkinson’s disease. It is unknown, however, which specific cell types are involved and how their activity changes during the course of the disease. In these experiments, we will use new technologies to study large groups of specific types of cortical neurons (for example, those that send fibers to the spinal cord) and explore how their activity and morphology change in animal models of chronic Parkinson’s disease.
Our hypothesis is that groups of cortical neurons that send fibers to the spinal cord, unlike those that send projections to the striatum, start to show abnormal activity and undergo morphological changes in connections that provide inputs to them when parkinsonism develops.
We will measure the anatomical and functional characteristics of neurons in the motor cortex, in animal models of slowly progressive Parkinson’s disease. Optical imaging methods as well as electrophysiologic recordings will allow us to measure the activity patterns of large groups of individual cortical neurons, while parallel anatomical studies will identify the reshaping of connections to different families of cortical neurons before and during the development of parkinsonism. Computational analysis will allow us to put the findings together in computer simulations that will help us to understand the cortical circuit abnormalities that contribute to Parkinson’s disease.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
A better understanding of how movement problems in Parkinson’s disease develop is key to developing more effective methods to control them. Characterizing the abnormalities in specific families of cortical neurons may allow us to develop new therapies that target the affected circuits through deep brain stimulation, pharmacologic, or genetic methods.
Next Steps for Development:
The results of these studies will guide the development of new therapeutic strategies (e.g., chemogenetic approaches), and optimization of deep brain stimulation methods, to disrupt abnormal cortical activity. Establishing the time course of anatomical changes, relative to disease progression, may provide insight into the appropriate timing for applying these strategies.