In several areas of the adult brain, notably the olfactory bulb, new neurons are generated and integrated into existing mature circuits. This observation raises questions about how an ongoing developmental process shapes adult brain circuitry and opens potential treatment avenues for neurological disorders such as traumatic brain injury, ischemia, depression, and degenerative diseases. In the networks where adult neurogenesis occurs the integration of adult-born neurons is modulated by activity. The experiments in this proposal are designed to address the hypothesis that adult-born neurons integrate into mature circuits in a competitive activity dependent manner. Specifically we will use lentiviral driven gene delivery to modulate the level of activity in a specific population of adult-born neurons in the olfactory bulb. Using these tools we will test whether activity directly causes enhanced integration of adult-born neurons in a cell autonomous fashion or whether integration is a competitive process in which the most active cells anywhere in the network have the highest chance of survival. These results will provide important insights into the role of activity in the integration and therapeutic potential of neural stem cells in mature functional brain circuits.
