Identification of a molecular basis for the juvenile sleep state / Leela Chakravarti Dilley.

Format:

Book

Thesis/Dissertation

Author/Creator:

Dilley, Leela Chakravarti, author.

Contributor:

University of Pennsylvania. Department of Cell and Molecular Biology, degree granting institution.

Kayser, Matthew S., degree supervisor.

Language:

English

Subjects (All):

Nanoscience.

Cellular biology.

Molecular biology.

Cell and molecular biology--Penn dissertations.

Penn dissertations--Cell and molecular biology.

Local Subjects:

Nanoscience.

Cellular biology.

Molecular biology.

Cell and molecular biology--Penn dissertations.

Penn dissertations--Cell and molecular biology.

Genre:

Academic theses.

Physical Description:

1 online resource (136 pages)

Contained In:

Dissertations Abstracts International 81-09B.

Place of Publication:

[Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2019.

Language Note:

English

System Details:

Mode of access: World Wide Web.

text file

Summary:

Sleep is a highly conserved behavior critical to nervous system function. Across species, sleep amounts are highest in young animals and taper with maturity. These ontogenetic changes to sleep have long been thought to facilitate brain maturation. Indeed, developmental sleep abnormalities are highly prevalent across neuropsychiatric disorders. However, knowledge of the genetic and molecular factors controlling early life sleep is lacking. Here, we use Drosophila to investigate the juvenile sleep state. Detailed behavioral characterization supports the idea that juvenile sleep represents a distinct behavioral state, uniquely evolved for the needs of a developing nervous system. Consistent with this, we find that sleep ontogenetic change is preserved in all studied short and long sleeping Drosophila mutants, suggesting that the molecular determinants of adult sleep duration do not regulate developmental sleep transitions. Through an RNAi-based screen, we identified the transcription factor pdm3 as the first known genetic regulator of sleep ontogeny. Increased sleep in young flies is normally driven by elevated activity of the sleep-promoting dorsal fan shaped body (dFSB). Loss of PDM3 leads to a premature increase in inhibitory wake-promoting dopaminergic (DA) synapses in the dFSB, reducing dFSB activity and preventing young flies from achieving the high sleep amounts normally observed. Pdm3 acts during the mid-pupal developmental stage to control DA projection ingrowth to this sleep region. Transcriptional analysis indicated that pdm3-mediated repression of the synaptogenesis gene Msp300 controls sleep ontogeny. Overall, this work demonstrates that juvenile sleep is a unique behavior subject to distinct genetic regulation, and provides the first insight into molecular cues governing sleep ontogeny. Further, our findings support the existence of a new class of developmentally-expressed sleep genes that orchestrate sleep circuit formation, raising the possibility that some primary sleep disorders are of neurodevelopmental origin.

Notes:

Source: Dissertations Abstracts International, Volume: 81-09, Section: B.

Advisors: Kayser, Matthew S.; Committee members: Amita Sehgal; Yuanquan Song; David Raizen; Gregory Bashaw.

Department: Cell and Molecular Biology.

Ph.D. University of Pennsylvania 2019.

Local Notes:

School code: 0175

ISBN:

9781392646007

Access Restriction:

Restricted for use by site license.

This item is not available from ProQuest Dissertations & Theses.

This item must not be sold to any third party vendors.