This item is under embargo and not available online per the author's request. For access information, please visit http://libanswers.wustl.edu/faq/5640.

Date of Award

Summer 8-15-2018

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Astrocytes are active partners in neural information processing. However, the roles of astrocytes in regulating behavior remain unclear. Because astrocytes have persistent circadian clock gene expression and ATP release in vitro, I hypothesized that they regulate daily rhythms in neurons and behavior. Here, I demonstrated that daily rhythms in astrocytes within the mammalian master circadian pacemaker, the suprachiasmatic nucleus (SCN), determine the period of wheel-running activity. Ablating the essential clock gene Bmal1 specifically in SCN astrocytes lengthened the circadian period of clock gene expression in the SCN and in locomotor behavior. Similarly, excision of the short-period CK1_ tau mutation specifically from SCN astrocytes also resulted in lengthened rhythms in the SCN and behavior. These results indicate that astrocytes within the SCN communicate to neurons to determine circadian rhythms in physiology and in wheel-running activity. As a first step to understanding how the two cell types interact, I attempted to delineate the circadian phase relationship of clock gene expression between neurons and astrocytes. With limited success, I will discuss both preliminary findings and challenges I faced. Lastly, I will present SCN single-cell transcriptomics data as a first step to understand properties of SCN astrocytes and diversity of SCN cell types. Clock genes enriched in SCN astrocytes identified by single-cell transcriptomics here can serve as a launching point to investigate how SCN astrocytes communicate to SCN neurons.

Language

English (en)

Chair and Committee

Erik Herzog

Committee Members

Paul Taghert, Joseph Dougherty, Steven Mennerick, Erik Musiek,

Comments

Permanent URL: 2020-08-23

Available for download on Monday, August 15, 2118

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