A Zebrafish Model to Study Microglial-Extracellular Matrix Dynamics During Synapse Development

2021 Seed Grant
Anna V. Molofsky, M.D., Ph.D.
University of California San Francisco

Carl & Marilynn Thoma Foundation Seed Grant

The connections between nerve cells- called synapses- are essential for all brain functions, including thinking, behavior, and movement. Impaired development of these synaptic connections can contribute to disorders like autism spectrum disorder (ASD), schizophrenia, and epilepsy. Our group studies a type of brain cell called microglia which are present in the brain but are also a part of the immune system. Microglia can help new synaptic connections to form and can remove synapses that are no longer needed. However, it is not currently possible to observe these processes happening in real time. In this project, we will develop tools and techniques to study microglia, synapses, and the ʻin betweenʼ spaces of the brain in a living animal. We will use zebrafish, a small, transparent fish that develops outside the body, thus can be visualized with a high powered microscope. Using zebrafish embryos, we can watch the brain developing, and directly examine the movements and connections between brain cells in real time. These studies will lead to new discoveries about how the brain’s immune cells promote healthy brain function, and suggest new therapies.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The Role of Microglial Lysosomes in Selective Neuronal Vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the Nervous System Constructs Internal Models of the External World
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the Orchestra of Movement—Functional Role of Striatal Astrocytes in Health and Disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…