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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Expanding neurons in the developing murine brain: effects on perinatal cortical histology and implications on cognition in adulthood

Darmis, Fragkiskos 23 September 2021 (has links)
Cognition is a trait of great evolutionary importance in complex organisms, but the driving factors of its evolution are still poorly understood. It is proposed that different formula variants of the encephalization index (brain to body weight ratio) might be able to serve as predictive indicators of intelligence between species, but this remains highly controversial, predominantly because of their inability to reliably validate empirical knowledge. Another proposed predictive index for intelligence has been the total neuron count in animals’ brains. There is, though, a lack of comparative and quantitative behavioral data in support of any of the proposed models, especially across non-human mammals. Total neuron count is controlled by the process of neurogenesis during development, which is directly involved in shaping brain’s dimensions. It is known that neural stem cells increasingly shift from proliferative divisions towards differentiating (or neurogenic) divisions during development. One possible approach to alter cortical topology is by manipulating the stem cell division in order to generate more neurons. It has previously been shown that one of the main factors known to influence the type of cell division mode is the length of the cell cycle and specifically the length of G1 phase. The main constituents driving progression through G1 phase are Cdk4 and Cyclin D1 (4D for simplicity) and overexpression of these proteins in neural stem cells results in a shortening of their cell cycle, leading to expansion of the progenitor cell pool at the expense of newborn neurons. Upon silencing 4D, development is allowed to continue normally and thus, the excess of progenitor cells ultimately contributes to an increased generation of neurons. Intriguingly, transient 4D overexpression during corticogenesis in transgenic mice leads to the development of brains with increased encephalization index as a result of an increase in the total neuron count, without altering cortical lamination or preventing cortical layering. In this study, I further characterize the effects of developmentally-induced 4D neurogenesis in the developing and adult mouse brain. Moreover, with the use of different cognitive tests designed to assess differences in processes such as learning, spatial navigation, motor coordination, and context iscrimination, I attempt to identify quantifiable changes in these processes between mice with increased neuron count and controls. I hypothesize that a general intelligence ranking between groups can be obtained by analyzing collective data from several tests. Altogether, my work provides a better understanding of the contribution of increased neurogenesis both in developmental processes of the cortex as well as in animal cognition and behavior.

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