Spicing up brain stem cells and brain function with neurotransmitters (SSA)

New neurons are continuously generated in the adult brain from neural stem cells found in particular niches, through a process called adult neurogenesis. Active retention of these neurons and enhancement of adult neurogenesis is thought to benefit brain functions and protect against dementia and depression. Therefore, there is an avid search for factors and molecules that can promote adult neurogenesis. Neurotrasmitters, such as Acetylcholine, typically mediate trans-synaptic communication between neurons and their target organs. However, they also seem to play an unexpected role in adult neurogenesis by modulating the proliferation and differentiation of neural stem cells. Indeed, elderly patients treated with anti-cholinergic drugs for other ailments, appear to be more susceptible to cognitive decline. In part, these unexpected roles appear to involve classical growth factors such as the Fibroblast Growth Factor signalling system.

This project aims to dissect the molecular partnerships that acetylcholine develops with growth factors to induce its beneficial effects on brain stem cells. This will be investigated using well-established in vitro model systems for neural stem cell growth, as well as brain slice cultures that preserve the stem cell niche architecture. In each of these systems, we will profile the key players and components, and using molecular and transgenic mouse models test their contribution and significance to adult neurogenesis. In addition to generic training skills, through these studies, the applicant will become proficient in a host of cellular and molecular techniques, including immunolabelling, gene-profiling and cloning, brain culture and high-resolution time-lapse imaging. Combined, these studies will prepare a candidate for a research career in molecular neurosciences.