Dr. William Zeiger


William Zeiger, MD, PhD

Name of Institution:

University of California – Los Angeles, Los Angeles, CA

Project Title:

Mechanisms of posterior cortical circuit dysfunction and cognitive impairment in a mouse model of PD

Investigator Bio:

Dr. Zeiger is a physician scientist in the Department of Neurology at the University of California – Los Angeles UCLA. He trained in the combined MD/PhD program at the University of Chicago Pritzker School of Medicine from 2005-2013. He completed his PhD in 2011, working in the laboratory of Dr. Gopal Thinakaran to study mechanisms of cellular calcium homeostasis in relation to neurodegeneration and amyloid-beta production. He then completed his medical degree in 2013, graduating with honors, and subsequently did residency training in Neurology at Johns Hopkins University and UCLA. Following residency, Dr. Zeiger completed a combined fellowship program at UCLA, doing clinical training in movement disorders and working as a post-doctoral research scholar with Dr. Carlos Portera-Cailliau.

Clinically, Dr. Zeiger works as a neurologist specializing in movement disorders, particularly Parkinson disease (PD) and atypical parkinsonian disorders. Dr. Zeiger also runs a neuroscience research lab focused on investigating cortical circuit dysfunction in mouse models of neurological disorders, in particular stroke and PD. His lab uses advanced, multimodal in vivo imaging techniques, circuit manipulations, and novel behavioral assays to understand how specific changes in the activity of neurons contribute to symptoms of these diseases and how brain circuits might be manipulated to treat these disorders.


The first objective is to study if, and how, a-Syn causes the dysfunction of brain cells that lead to thinking and memory problems. The second objective is to test whether we can change the activity of certain brain cells to slow down or stop the accumulation of a-Syn.


Over time, many patients with PD develop problems with thinking and memory and these can progress to dementia. Many patients with PD show an accumulation of a protein called alpha-synuclein (a-Syn) in the brain and it is believed that this may be important for some of the symptoms of PD. However, we do not understand fully how the accumulation of a-Syn might lead to thinking and memory problems in people with PD.


We will study how a-Syn causes problems with thinking and memory by using advanced microscopes to directly measure the activity of brain cells in living mice. We will do this in mice in which we have caused a-Syn to accumulate over time. We will then see if changes in the activity of brain cells lead to problems with thinking in the mice that are similar to those experienced by persons with PD. To test whether we can slow down the accumulation of a-Syn in the brain, we will use genetic tools to increase or decrease the activity of specific brain cells in particular regions of the brain. We will then measure the amount of a-Syn that accumulates over time in brain regions that are important for thinking and memory problems in person with PD.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:

We hope that by understanding how a-Syn accumulation affects the activity of brain cells and the development of thinking and memory problems in PD, we may discover new opportunities to specifically treat these disabling symptoms. Moreover, by learning the effects of changing the activity of brain cells in specific regions of the brain, we can potentially design clinical trials that do this in humans, with the goal of slowing or stopping the progression of PD.