The adult brain has the ability to structurally and functionally adapt to changes in its environment. Examples of these adaptations
are the addition of new neurons to neurogenic regions such as the hippocampal dentate gyrus, termed adult hippocampal neurogenesis,
and alterations in neuronal connections at synaptic sites. Both of these forms of plasticity are heavily regulated at multiple
molecular levels, not all of which are fully understood.
Concerning AHN, a number of crucial events occur before newly
born neurons in the adult hippocampus can functionally contribute to the pre-existing network. Exit of the neural precursor
cells (NPCs) from their quiescent state, proliferation, fate decisions and selection through apoptosis are the changes that
together control the neurogenic cascade. This plethora of events can all take place within a time-span of several days, and
as such require rapid yet carefully orchestrated changes in the molecular machinery of these cells. This coordinated action
can be achieved through multiple layers of molecular control, many of which are epigenetic, such as alterations in gene promoter
DNA methylation and microRNA-mediated control of mRNA translation. Furthermore, specific alterations in any of these layers
of molecular control, and in the corresponding cellular phenotypes, can also be induced by cell extrinsic factors such as
circuit hyper-activation, alterations in glucocorticoids or during aging.
Therefore, the overall aim of this thesis is
the identification of novel epigenetic mechanisms governing phenotypical changes of NPCs and newborn neurons such as quiescence,
proliferation, apoptosis and differentiation, induced by these aforementioned cell extrinsic factors.