Experiences alter brain cells, causing structural and functional changes that are responsible for the ability to learn, think, detect, and respond to stimuli with greater sensitivity and coordination. Discovering the precise nature and mechanisms of these changes are necessary in order to understand how the brain works. This study will carefully examine an under-explored aspect of this problem: when, where, and how experiences cause changes to glial cells and to the ways in which glial cells interact with neurons. The study will utilize embryonic and larval zebrafish as a model organism. Zebrafish possess both neurons and glia housed within a transparent body and skeleton, yet they share common mechanisms of neural development with other vertebrates including humans, and are cost-efficient to work with. The outcomes of this study are expected to reveal how functional relationships between neurons and glia are remodeled by experiences, and to discover new molecules and cellular pathways responsible for these transformations. High school students, both future-first generation college students and students from underrepresented groups in STEM professions, will be actively involved as a means to encourage college applications to STEM programs. High school classrooms and community members will learn about the importance of model organisms through hands-on outreach activities.
Myelination is traditionally viewed as an intrinsic developmental program proceeding independently of external experiences. This paradigm is shifting; a new model of adaptive myelination proposes that experiences influence myelination, and adaptive changes in myelination alter circuit activity and spike timing in a way that is necessary for normal learning and cognition. An outstanding gap in knowledge is whether adaptive changes involve shifts between specific circuits and axon subtypes targeted for myelination. The purpose of this project is to identify the specific axon subtypes undergoing adaptive shifts in myelination, to determine the oligodendrocyte cell behaviors mediating these shifts, and to dissect molecular mechanisms of axon subtype-specific recognition. Studies will utilize larval zebrafish and in vivo imaging to directly observe changes to oligodendrocyte-axon interactions occurring in response to manipulations of gene function and neural activity. Expected outcomes will advance understanding of how oligodendrocytes and myelin remodeling contribute to neural plasticity.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
