Cellular mechanisms regulating adult neurogenesis and olfactory perception in mice

In the adult mammalian brain, neural stem cells persist in the subventricular zone and the hippocampus, producing new functional neurons throughout life. Whether and how adult neurogenesis maintains brain function remains highly debated. This question is of primary interest due to the potential therapeutic use of adult neurogenesis in treating neurodegenerative disease. Furthermore, understanding the functional impact of adult neurogenesis on the sense of smell may help deciphering the neural code underlying odor recognition. In this thesis work, we impaired adult neurogenesis using molecular, transgenic and focal irradiation approaches. We assessed olfactory function using in vitro and in vivo electrophysiology, in vivo optical imaging and behavioral psychophysical measurements. We show that reducing the number of newborn interneurons decreases the level of synchronized firing of the projection neurons and leads to impaired olfactory discrimination performance in behaving mice. By isolation of specific olfactory bulb cellular populations, we provide a series of genetic markers differentiating newborn cells from mature neurons that mediate the observed function of olfactory neurogenesis. This thesis work demonstrates that adult neurogenesis represents a new form of plasticity that supports brain function, controlling olfactory information processing already at the first central relay. Finally our data give also insights about the cellular and molecular mechanisms occurring in the olfactory bulb network controlling sensory perception, and help define key genes in the neuronal maturation process.