Intrinsic neuronal activity during migration controls the recruitment of specific interneuron subtypes in the postnatal mouse olfactory bulb

Abstract

Neuronal activity has been identified as a key regulator of neuronal network development, but the impact of activity on migration and terminal positioning of interneuron subtypes is poorly understood. The absence of early subpopulation markers and the presence of intermingled migratory and post-migratory neurons makes the developing cerebral cortex a difficult model to answer these questions. Postnatal neurogenesis in the subventricular zone offers a more accessible and compartmentalized model. Neural stem cells regionalized along the border of the lateral ventricle produce two main subtypes of neural progenitors, granule cells and periglomerular neurons that migrate tangentially in the rostral migratory stream before migrating radially in the OB layers. Here we take advantage of targeted postnatal electroporation to compare the migration of these two population. We do not observe any obvious differences regarding the mode of tangential or radial migration between these two subtypes. However, we find a very striking increase of intrinsic calcium activity only in granule cell precursors when they switch from tangential to radial migration. By decreasing neuronal excitability in granule cell precursors, we find that neuronal activity is critical for normal migratory speed at the end of tangential migration. Importantly, we also find that activity is required for normal positioning and survival of granule cell precursors in the OB layers. Strikingly, decreasing activity of periglomerular neuron precursors did not impact their positioning or survival. Altogether these findings suggest that neuronal excitability plays a subtype specific role during the late stage of migration of postnatally born olfactory bulb interneurons.