Memory plays an essential role in the survival of all living organisms, and thus understanding the many factors which influence memory is of critical importance. One such factor is that of the circadian clock, an internal biological timekeeper composed of a conserved molecular core clock and, in invertebrates such as Drosophila and mammals alike, a neural core clock circuit in the brain. Collectively, the circadian clock acts to optimize an organism’s biological and behavioral processes—such as memory—by directing their rhythmic cycling with a periodicity set by external cues such as the sun. Circadian effects on human memory have been observed for over 100 years, and particular components of the molecular clock have been implicated in this phenomenon in both mammalian and Drosophila models. However a neural pathway by which the clock regulates memory has yet to be discovered. This dissertation examines a role for the core clock circuit signaling peptide Pigment-dispersing factor (PDF) and its canonical receptor PDFR in regulation of memory in the fruit fly Drosophila melanogaster. It was found that the PDF signaling pathway is required for associative olfactory short- and long-term appetitive memory. Its requirement for appetitive STM is time-of-day independent, though the magnitude of its contribution is not, and evidence of a latent independent oscillator was found in wildtype flies. PDF can regulate locomotor activity and memory independently, and its effects on appetitive STM are achieved by signaling to targets outside of the core clock circuit and the memory-relevant mushroom body. The clock-based PDF signal is required for aversive olfactory STM as well but likely acts through a second unknown PDF receptor to perform this role, demonstrating a valence-specific level of control by the clock over memory. Behavioral and functional imaging screens to identify the neural target of PDF involved in clock-memory regulation were also conducted, producing an acquisition and data analysis pipeline useful in future studies. Lastly, a pedagogical tool was developed to train undergraduate Drosophila researchers in practical application of balancer chromosomes; this was expanded into FlyBuilder, a multimodal three-part curriculum which allows dry-lab hands-on application of Mendelian genetics, and can be integrated into a variety of undergraduate courses.
|Advisor:||Griffith, Leslie C.|
|Commitee:||Rosbash, Michael, Garrity, Paul A., Kaun, Karla R.|
|School Location:||United States -- Massachusetts|
|Source:||DAI-A 82/3(E), Dissertation Abstracts International|
|Subjects:||Neurosciences, Science education|
|Keywords:||Circadian, Memory, Mendelian genetics, Peptide|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
The supplemental file or files you are about to download were provided to ProQuest by the author as part of a
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
Copyright of the original materials contained in the supplemental file is retained by the author and your access to the
supplemental files is subject to the ProQuest Terms and Conditions of use.
Depending on the size of the file(s) you are downloading, the system may take some time to download them. Please be