Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

You searched for id:"oai:etd.ohiolink.edu:case1473440530837021". One record found.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters

1. Whitney, Meredith Sorenson, Deneris. Novel Targeting of Adult Brain Serotonin Reveals New Roles in Behavior.

Degree: PhD, Neurosciences, 2017, Case Western Reserve University

Serotonin (5-HT) is a crucial neuromodulator linked to many psychiatric disorders, including major depression, post-traumatic stress disorder, generalized anxiety disorder, obsessive compulsive disorder, and suicide. Yet, after more than six decades of study, its role in behavior remains poorly understood, in part, because of a lack of techniques to specifically target 5-HT synthesis in the adult brain. Here, we have developed a genetic approach that reproducibly achieves near-complete elimination of 5-HT synthesis from the adult ascending 5-HT system by stereotaxic injection of an adeno-associated virus expressing Cre recombinase (AAV-Cre) into the midbrain/pons of mice carrying a loxP-conditional tryptophan hydroxylase 2 (Tph2) allele. We investigated the effect of deficient brain 5-HT synthesis on behavior and discovered a unique composite phenotype. Surprisingly, adult 5-HT deficiency did not affect anxiety-like behavior, but resulted in a robust hyperactivity phenotype in novel and home cage environments. Additionally, loss of 5-HT led to an altered pattern of circadian behavior characterized by an advance in the onset and a delay in the offset of daily activity, thus revealing a requirement for adult 5-HT in the control of daily activity patterns. Notably, after normalizing for hyperactivity, we found that the normal ~2-hour break in nocturnal activity (siesta), a period of REM and NREM sleep, was absent in all animals in which 5-HT deficiency was verified. Our findings identify adult 5-HT as a requirement for siestas and implicate it in the regulation of sleep-wake homeostasis. Preliminary results from other testing suggests that adult 5-HT may also be involved in regulating immune gene expression in the brain, peripheral metabolic homeostasis, CNS norepinephrine levels, and autonomic functions. In addition to demonstrating a specific role for adult 5-HT in controlling locomotor activity, daily circadian patterns, and siestas, our results highlight the importance of our adult-specific 5-HT-synthesis-targeting approach in understanding 5-HT’s role in behavior. Advisors/Committee Members: Deneris, Evan (Advisor), Silver, Jerry (Committee Chair).

Subjects/Keywords: Behavioral Sciences; Neurosciences; Neurobiology; circadian behavior; hyperactivity; serotonin; tryptophan hydroxylase; siesta

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Whitney, Meredith Sorenson, D. (2017). Novel Targeting of Adult Brain Serotonin Reveals New Roles in Behavior. (Doctoral Dissertation). Case Western Reserve University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1473440530837021

Chicago Manual of Style (16th Edition):

Whitney, Meredith Sorenson, Deneris. “Novel Targeting of Adult Brain Serotonin Reveals New Roles in Behavior.” 2017. Doctoral Dissertation, Case Western Reserve University. Accessed November 17, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1473440530837021.

MLA Handbook (7th Edition):

Whitney, Meredith Sorenson, Deneris. “Novel Targeting of Adult Brain Serotonin Reveals New Roles in Behavior.” 2017. Web. 17 Nov 2017.

Vancouver:

Whitney, Meredith Sorenson D. Novel Targeting of Adult Brain Serotonin Reveals New Roles in Behavior. [Internet] [Doctoral dissertation]. Case Western Reserve University; 2017. [cited 2017 Nov 17]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1473440530837021.

Council of Science Editors:

Whitney, Meredith Sorenson D. Novel Targeting of Adult Brain Serotonin Reveals New Roles in Behavior. [Doctoral Dissertation]. Case Western Reserve University; 2017. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1473440530837021

.