UC San Diego

Newborn neurons are generated and incorporated into existing neural circuitry throughout the lifetime of adult mammals. In rodents, the major targets of neurogenesis are the dentate gyrus of the hippocampus and the olfactory bulb. In the olfactory system, neural precursor cells (NPCs) generated in the lateral ventricle migrate via the rostral migratory stream and radiate into the granule and glomerular layers of the olfactory bulb. Throughout adulthood, NPCs give rise to local inhibitory neurons, granule cells and periglomerular cells, which receive glutamatergic inputs in the bulb. However, the properties of NPCs and the mechanisms that regulate their movement are not thoroughly understood. Here we show that olfactory bulb NPCs express Ca²⁺-permeable AMPA receptors (AMPARs), and that activation of these receptors inhibits NPC motility. Glutamate spillover from distant excitatory synapses in bulb slices is sufficient to activate NPC AMPARs and inhibit their migration. Surprisingly, this effect on migration is independent of Ca²⁺ influx through AMPARs. In many other systems of neural cell migration, intracellular Ca²⁺ signaling plays a critical role in cell motility. Therefore, this Ca²⁺-independent inhibition of NPC migration is a highly unique aspect of olfactory bulb neurogenesis. To further test the relationship between intracellular Ca²⁺ and migration in NPCs, we characterize the intrinsic membrane properties of the cells and show that NPCs are capable of firing regenerative Ca²⁺ spikes, and that they express L-type voltage-sensitive Ca²⁺ channels (VSCCs) that underlie spontaneous elevations in intracellular Ca²⁺. Consistent with our finding that AMPAR -mediated inhibition of migration is independent of Ca²⁺ signaling, modulation of L-type VSCCs in NPCs does not alter migration