VIRUS MEDIATED EXPRESSION OF DOUBLE FLOXED GENESIN NEURONS OF THE DENTATE GYRUS: The exploration of a new method to ablate adult born neurons

Abstract

Adult neurogenesis is a process occurring in the mammalian dentate gyrus (a region in the hippocampus). Various lines of evidence show that this process is involved in learning and memory. The exact role of the adult born neurons is unclear though. In this master thesis we present a novel method to investigate the role of adult born neurons. The method aims to ablate adult born neurons at a time point after mitosis. Where existing ablation methods only stop the process of adult neurogenesis (i.e. prevent the neurons from being born), this method ‘tags’ adult born neurons and enables ablation after these neurons have matured. The tagging occursby virus mediated expression of the diphtheria toxin receptor, while the actual ablation is done by injection with the diphtheria toxin. With this novel feature of ablation after maturation, the method can shed new lighton the exact role of adult born neurons in learning and memory (whether this is acquisition, consolidation orretention of a memory). Before we can use the method though, we need to test if it is feasible. This thesis describes the first explorations of this novel method of ablation. We have established a proof of concept. Besides this, we found an indication that the method is specific for adult born neurons. However, as it is, the method is in all probability not effective enough to have any effect on learning and memory. We conclude by suggesting improvements to increase the efficacy.