The role of spontaneous/sensory-driven activity for migration and integration of adult-born neurons of the mammalian olfactory bulb

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Prior to integration into the local neuronal circuitry adult-born neural stem cells of the mammalian olfactory bulb (OB) travel a long distance within the rostral migratory stream (RMS) and the OB. The migration of neural precursors within the RMS is characterized in much detail, but until recently little was known about their migration within the OB. Our recent study characterized in vivo migration patterns of adult-born cells within the OB and revealed a unique long-range migration of the juxtaglomerular neurons (JGNs) within the destination layer. JGNs retain the ability to move for at least 3 weeks after their arrival at the destination layer (a developmental period which we name a pre-integration phase) and undergo a lateral migration while retaining and remodeling an elaborated dendritic tree, responding to odorants with big calcium transients and exhibiting large spontaneous fluctuations in the intracellular calcium concentration. Building on our previous results and using recently developed molecular tools, in the current proposal we aim to characterize in vivo cellular/molecular mechanisms governing the migration and differentiation of adult-born JGNs during the pre-integration phase and to understand the role of the spontaneous/sensory-driven activity for these processes. To do so we are going to address the following specific goals: (i) characterization of the role of spontaneous/sensory-driven activity for neuronal migration and integration, (ii) understanding the role of spontaneous/sensory-driven activity for differentiation of adult-born cells, (iii) deciphering the mechanisms underlying survival/elimination of adult-born neurons.The experiments outlined in the current proposal will provide a unique opportunity to visualize in vivo activity patterns of migrating neurons during the pre-integration phase and to learn how the interplay between the spontaneous and sensory-driven activities controls migration, differentiation and survival of adult stem cells, as well as their decision when and where to integrate.