Off-campus UMass Amherst users: To download campus access dissertations, please use the following link to log into our proxy server with your UMass Amherst user name and password.
Non-UMass Amherst users: Please talk to your librarian about requesting this dissertation through interlibrary loan.
Dissertations that have an embargo placed on them will not be available to anyone until the embargo expires.
Author ORCID Identifier
N/A
AccessType
Open Access Dissertation
Document Type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Neuroscience and Behavior
Year Degree Awarded
2015
Month Degree Awarded
September
First Advisor
Eric L. Bittman
Second Advisor
Tanya Leise
Third Advisor
William Schwartz
Fourth Advisor
Courtney Babbitt
Subject Categories
Behavioral Neurobiology | Molecular and Cellular Neuroscience
Abstract
The recently discovered circadian mutant hamster duper has a short period of ~23 hours and exhibits exaggerated phase shifts in response to a 15-min light pulse. To increase the understanding of the duper mutation, I performed behavioral, neurobiological, and genetic experiments. Behavioral studies using photic and non-photic stimuli found that large phase shifts exhibited by duper hamsters are specific to photic cues, but not to phase. Additionally, 2/3 of duper hamsters, but no WTs, displayed transient ultradian wheel-running patterns when transferred from light to dark at CT 18. This suggests that the mutation may weaken coupling among components of the circadian pacemaker. Anatomical and immunocytochemical analysis of the SCN was used to examine the neurobiological mechanisms of large light-induced phase shifts in dupers. Brains were collected from duper and WT hamsters at CT 12 and 15 as well as 1, 2, 3, 6 and 9 hours following a light pulse, or control handling, at CT 15. Surprisingly, the only difference in PER1 (a core clock protein) expression in the SCN between dupers and WTs was seen 2-hours after a light pulse; duper hamsters displayed a significantly greater percentage of retinorecipient VIP cells co-labeled with PER1 compared to WTs. Additional differences between genotypes occurred 9 hours after CT15 (controls). In the SCN, the number of PER1-ir cells was significantly greater in WT than duper hamsters, however this finding was reversed in the PVN. This anatomical mismatch suggests the mutation may affect signaling between the SCN and extra-SCN oscillators. Finally, to identify the genetic basis of the duper phenotype, I crossed dupers with a novel ecotype in order to perform fast homozygosity mapping. Duper transmitted onto the novel ecotype with the predicted Mendelian inheritance of phenotype. I collected DNA from F2 duper hamsters, and expect fast homozygosity mapping will identify candidate genetic regions of the duper mutation. Additional behavioral experiments in F2 dupers demonstrated that duper hamsters are resistant to jet lag. As duper is a unique circadian mutation, understanding of the behavioral phenotype, neurobiological mechanism, and genetic basis of the duper mutation will greatly increase our knowledge of the circadian system.
DOI
https://doi.org/10.7275/7525276.0
Recommended Citation
Manoogian, Emily Nicole Corbett, "Behavioral, Neurobiological, and Genetic Analysis of the Circadian Mutant Duper" (2015). Doctoral Dissertations. 509.
https://doi.org/10.7275/7525276.0
https://scholarworks.umass.edu/dissertations_2/509