Authors

Soyoung Rhee

Type

Text

Type

Dissertation

Advisor

Ge, Shaoyu | Talmage, David | Takemaru, Ken-ichi | Sahay, Amar.

Date

2015-12-01

Keywords

Adult born neurons, Hippocampus associated behavior, Migration, Primary cilia | Neurosciences

Department

Department of Molecular and Cellular Pharmacology.

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/76525

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

Adult born neurons in the hippocampal dentate gyrus start to assemble primary cilia at 14 days after their birth. At 21 days, all newborn neurons show a typical primary cilium. Although this small microtubule-based structure has been shown to be important for early neuronal development, its physiological/behavioral roles remain elusive. Therefore, I set out to investigate both behavioral and physiological functions of primary cilia in immature and mature dentate granule cells (DGCs) of the adult brain. After selectively knocking out IFT20 to ablate primary cilia from mature DGCs, I found defects of hippocampal spatial and cognitive memory, suggesting a crucial role of primary ciliary in mature neurons. I further observed that ablation of primary cilia in mature DGCs increased long-term potentiation in mossy fiber pathway. The decrease of synaptic plasticity after primary cilia depletion in mature DGCs may consequently increase the portion of synaptic activity of young adult born DGCs. Furthermore, my research indicated that primary cilia modulate early tangential dispersion and radial migration of adult born DGCs. Taken together, my thesis work suggests that primary cilia of DGCs play critical roles in regulating neuronal migration of newborn neurons and physiological/behavioral activities of mature neurons. These findings will facilitate us in understanding the role of primary cilia in neuronal development and function, as well as molecular mechanisms for ciliopathies. | 121 pages

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