Investigator:
William Zeiger, MD, PhD
Name of Institution:
The Regents of the University of California, Los Angeles
Project Title:
Neuronal microcircuit mechanisms of posterior cortical dysfunction and cognitive impairment in a mouse model of Parkinson’s disease
Investigator Bio:
Dr. Zeiger is a physician-scientist in the Department of Neurology, Movement Disorders Division, at UCLA. Dr. Zeiger attended the University of Illinois at Urbana-Champaign where he majored in Molecular and Cellular Biology. He then completed the MD-PhD program at the University of Chicago. His doctoral research focused on understanding the cell biology of the stress-induced protein Stanniocalcin 2 and the role of calcium homeostasis in regulating amyloid beta production. Dr. Zeiger completed clinical residency training in neurology at the Johns Hopkins Hospital and UCLA. He then did a fellowship, specializing in movement disorders at UCLA and completing post-doctoral research in the laboratory of Dr. Carlos Portera-Cailliau. Dr. Zeiger has expertise in the diagnosis and medical treatment of movement disorders, including Parkinson’s disease (PD), atypical Parkinsonism, tremors, and dystonia, among others. His research interest includes understanding mechanisms of cortical circuit function in the healthy brain and how dysfunction of cortical circuits contributes to pathophysiology and symptoms of neurologic disorders such as stroke and PD.
Objective:
To understand how alpha-synuclein (a-syn) contributes to thinking and memory problems and, specifically, problems with processing of visual information.
Background:
Many people with PD experience impairments in thinking and memory. More specifically, people with PD have difficulty processing visual information and can even experience troubling visual hallucinations. Currently there are no therapies that can slow down or prevent the progression of problems with thinking and memory in PD. The abnormal clumping of the protein a-syn in the brain cells that are responsible for thinking and memory likely plays a role in causing these problems, but precisely if, or how, a-syn accumulation contributes has not been worked out.
Methods/Design:
Here, we will use mice to model the problems that arise with thinking and memory in people with PD. We will inject a-syn into a part of the brain responsible for processing visual information. We will then use specialized tools and microscopes to measure the activity of different types of brain cells while mice perform a visual processing task. In a second study, we will try to understand how a-syn might get to brain regions involved in visual processing in the first place. We will use genetic tools to manipulate the activity of certain brain cells to test how changes in brain activity can cause a-syn to spread to regions of the brain important for thinking and memory.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
These studies will help us understand the role that a-syn plays in the development and progression of thinking and memory problems in people with PD. We will be able to see, for the first time, how a-syn can affect the activity of different brain cells in a living animal. We will then have a better understanding of how these changes affect a person’s ability to process visual information. We will also understand how changes in the activity of brain cells can affect the way a-syn spreads to parts of the brain important for thinking and memory. This information will help us design treatment strategies to try to restore the function of brain cells affected by a-syn.