Thesis defense Lidiane Pereira Garcia (Donders series 392)

9 July 2019

Promotores: prof. dr. J. Homberg, prof. dr. G. Martens
Co-promotor: dr. S. Kolk

Molecular dissection of prefrontal cortex development in health and disease:How serotonin makes up our mind

Dynamic events that occur during the early stages of cortical brain development eventually define behavior in adult life. The development of the prefrontal cortex follows a sequence of events that include cell proliferation, migration and differentiation, and the formation of neural connections. After birth, the prefrontal cortex continues to develop and specializes in the regulation of our more complex brain functions. During corticogenesis the neural connections are refined and modulated by a complex program of gene expression patterns combined with environmental influences. In these neurodevelopmental processes,  serotonin plays a major role. During embryonic development serotonin is a neurotrophic factor that controls cell proliferation, migration and survival, while in adult life it is a potent neurotransmitter regulating behavior. Therefore, the levels of serotonin are tightly regulated throughout life. The aim of this thesis was to investigate how changes in serotonin levels, by genetic or pharmacological manipulation (e.g. by the HIV drug efavirenz), influence the mechanisms that control the development of the medial prefrontal cortex. In addition, we identified the association of the serotonergic system with other systems, such as the catecholaminergic system, and how they together affect the stages of corticogenesis during neurodevelopment. Finally, we examined how these prenatal changes are reflected in postnatal and adult behavior.