Understanding the relationship between gene networks, neurons, and circuits that determine behavior is a fundamental problem in neuroscience. The brains biological clock the suprachiasmatic nucleus (SCN) is an excellent model system in which to study this crucial problem. SCN neurons possess daily molecular transcriptional/translational feedback loops and exhibit rhythms in spontaneous action potential frequency. The synchronized output of the SCN neural network ultimately dictates circadian behavior and physiology. A key unsolved question in circadian neurobiology is how these rhythms interact to form a coherent pacemaker. To address this question, I combined electrophysiology, real-time imaging of gene expression, SCN-specific optogenetic manipulation of neuronal firing, and monitoring of locomotor activity to elucidate the links between the molecular and electrical rhythms that comprise the brains biological clock and their circadian behavioral output. I found that optogenetic induction or suppression of firing rate within SCN neurons is sufficient to reset the phase and alter the period of the molecular clockworks, that this resetting requires action potentials and network communication, and that in vivo optogenetic stimulation of the SCN entrains locomotor activity rhythms. Additionally, the expression of the clock gene Period1 is necessary for the coordination of molecular and electrical rhythms in SCN neurons. Thus, I conclude that there is a bidirectional relationship between circadian rhythms in gene expression and electrical activity in SCN neurons such that firing rate is both an output of and an input onto the molecular clock.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-02272015-132732 |
| Date | 17 March 2015 |
| Creators | Jones, Jeffrey Robert |
| Contributors | Danny G. Winder, Christopher S. Colwell, Terry L. Page, Douglas G. McMahon |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-02272015-132732/ |
| Rights | restrictone, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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