Impact of Dopamine Alteration on Brain-Wide Functional Connectivity at Cellular Resolution
Abstract
The brain displays remarkable plasticity that enables learning and behavioral modifications in response to changes in life. In the case of Parkinson s disease (PD), however, plasticity may result in mixed blessings, including delayed diagnosis despite loss of a majority of dopamine neurons and debilitating side effects, including dyskinesia and impulse control disorders associated with dopamine replacement therapies. Advancements in science and technologies have allowed us to gain insights into brain network dynamics through imaging such as fMRI. Changes at the level of molecules and synapses are observable in cell cultures and animal models. However, these two bodies of knowledge remain disconnected. The aim of this application is to harvest the unique strength of a vertebrate model organism, larval zebrafish, to uncover brain plasticity at both systems level and cellular resolution. The proposed work relates to the specific Focus Area "Mechanisms of neuroplasticity in the Parkinson s disease brain." In the short term (3-5 years), this application aims to reveal critical mechanisms of neuroplasticity upon alterations of dopamine homeostasis. We will uncover network connectivity dynamics and cell types that drive such network dynamics. In the long term (5-10 years), our findings may lead to better early diagnosis tools and better treatments for side effects associated with dopamine replacement therapies. They may be in the form of computational algorithms, molecular, and pharmacological agents.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810176
Entities
People
- Su Guo
Organizations
- United States Army
- University of California, San Francisco