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theses

Within brain, rhythmic and spontaneous molecular cascades determine behavior. We used multiple methods of analysis to quantify several of these molecular cascades. The protein S100B acts as a bimodal calcium transduction switch in retinal cells involved with circadian rhythm entrainment. We show that S100B knockout mice exhibit a secondary circadian rhythm during intervals of photic entrainment. In another investigation, we searched for behavioral rhythms shorter than a day through analysis of the electroencephalogram (EEG). Using two separate methods, we show evidence for a short ultradian rhythm (SUR) in rats and mice correlative with sharp decreases in delta EEG activity and non-rapid-eye movement (non-REM) sleep. We also show the first semi-automated detection of a behavioral SUR using EEG data, which may provide insight into metabolic oscillations within brain tissue separate from the transcription/translation feedback loops governing circadian rhythms. In brain, extracellular adenosine accumulates during periods of wakefulness and diminishes after periods of non-REM sleep. We measured EEG and locomotor activity in mice lacking CD73, an enzyme involved with conversion of adenosine triphosphate (ATP) into adenosine. We show that CD73 knockout mice exhibit different amounts of wakefulness and REM sleep compared to wild-type mice, results consistent with a role of adenosine in sleep. Thyroid hormones also affect sleep. A dysthyroid state can induce sleep disturbance, lethargy, anxiety, or other symptoms. We injected 3-iodothyronamine (T1AM), a decarboxylated thyroid hormone derivative, into the preoptic region of adult male rats and collected EEG to quantify post-injection sleep. T1AM causes sleep fragmentation and, contrary to our hypothesis, decreased sleep in a similar way to thyroid hormone, which may be due to shared mechanisms of sleep regulation. We also demonstrate the existence of two new high-frequency EEG bands which vary in relation to sleep behavior in rats. Finally, we demonstrate that nicotinic acetylcholine receptors (nAChRs), which contribute to electrical activity regulation in brain, are inhibited by triiodothyronine (T3), a thyroid hormone, and pregnenolone sulfate, a neurosteroid with similar molecular properties. These data give new insight into the structure activity relationship of neurosteroids relative to nAChRs and to other related receptors in the brain.

ETD_9217

Ph.D.

Includes bibliographical references

by Steven Moffett

doi:10.7282/T30R9T01

ETD doctoral

The author owns the copyright to this work.