The production of new neurons in the hippocampus is thought to underpin aspects of learning and memory. Defining how neurogenesis is regulated is central to our understanding of the learning process and to the future development of neurogenic-based therapeutics aimed at ameliorating cognitive loss.
Recently, we identified a large precursor pool in the dentate gyrus of the mouse hippocampus, including a small number of true stem cells, which is normally dormant but can be activated by depolarizing levels of K+ to produce large numbers of neurogenic neurospheres. In situ stimulation of the perforant pathway also activates this precursor population and leads to an increase in newly born neurons. Importantly, this population can be activated in the aged mouse, uncovering the potential for significant neurogenesis in the ageing brain, and the opportunity to reverse cognitive loss which accompanies ageing.
Further, synaptic activity stimulates precursor activity through the release of a number of soluble factors and the neurotransmitter, norepinephrine (NE). These factors act directly on the precursors with NE activating through a novel adreno-receptor pathway. Interestingly, different stimuli led to the activation of different pools of precursors and stem cells, suggesting production of hippocampal neurons in the dentate gyrus with distinct properties may reflect the type of stimulation. This provides a mechanism by which the functional capacity and the number of newly generated neurons can be directly influenced by specific environmental stimuli.