Team Wichmann

Study Rationale: 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 (PD). It is unknown, however, which specific cell types are involved and how their activity changes during the course of the disease. In these experiments, Team Wichmann 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 PD.

Hypothesis: Team Wichmann’s 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.

Study Design: Team Wichmann will measure the anatomical and functional characteristics of neurons in the motor cortex in animal models of slowly progressive PD. Optical imaging methods as well as electrophysiologic recordings will allow the team 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 Team Wichmann to put the findings together in computer simulations that will help them to understand the cortical circuit abnormalities that contribute to PD.

Impact on Diagnosis: A better understanding of how movement problems in PD develop is key to developing more effective methods to control them. Characterizing the abnormalities in specific families of cortical neurons may allow researchers to develop new therapies that target the affected circuits through deep brain stimulation, pharmacologic, or genetic methods.