The adult hippocampus is a brain region fundamental in regulating key aspects of cognition and emotional behavior. It is also a region endowed with prominent forms of plasticity throughout life. One such example involves the hosting of stem cells which are capable to generate life-long new neurons that incorporate into and modify the pre-existing circuitry. However, the mechanisms underlying this extended form of plasticity, in particular in response to injury or to individuals experiences, remain unclear. This project aimed at developing innovative approaches to investigate the energy constrains that regulate the plasticity of adult neurogenic circuits. For this purpose, we focused on how certain structural and functional aspects of mitochondria – key organelles controlling cellular energy metabolism – may regulate the process of adult neurogenesis and the plasticity of associated circuits. For this, we investigated the role played by the mitochondrial network in driving significant changes along the lineage that bring a neural stem cell to become a fully-functional new neuron, that is, in modulating the extent of neurogenesis in relation to certain experiences. As neurogenesis is an exceptionally rare event in the adult mammalian brain, addressing this main objective may pave the way to regenerative approaches following brain injury or disease. During our investigations we revealed that mitochondria execute important forms of plasticity underling the activity of neural stem cells and their neuronal progeny, with key implications for approaches meant to ameliorate brain repair following brain damage.
