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.Significance StatementWhile neuronal activity is a critical factor regulating different aspects of neurogenesis, it has been challenging to study its role during the migration of different neuronal subpopulations. Here, we use postnatal targeted electroporation to label and manipulate the two main olfactory bulb interneuron subpopulations during their migration: granule cell and periglomerular neuron precursors. We find a very striking increase of calcium activity only in granule cell precursors when they switch from tangential to radial migration. Interestingly, blocking activity in granule cell precursors affected their migration, positioning and survival while periglomerular neuron precursors are not affected. These results suggest that neuronal activity is required specifically for the recruitment of granule cell precursors in the olfactory bulb layers.

Endogenous but not sensory-driven activity controls migration, morphogenesis and survival of adult-born neurons in the mouse olfactory bulb

“…Cumulative evidence suggests that the aforementioned molecular pathways (Figure 7I) govern the development and maturation of different kinds of neurons during neonatal as well as adult neurogenesis. Indeed, (i) the pCREB-mediated signaling pathway is critically important for survival and morphological maturation of adult-born cells both in the hippocampus and the OB (Herold et al, 2011;Jagasia et al, 2009); (ii) Ca 2+ -dependent CRTC1 signaling is required for dendritic growth of neonatal cortical neurons (Li et al, 2009); and (iii) L-type channel-mediated spontaneous Ca 2+ signaling is critical for migration and survival of neonatal OB GCs (Stéphane et al, 2020). Moreover, modification of cell-intrinsic neuronal activity and associated spontaneous Ca 2+ transients by either overexpression/blockade of different voltage-gated Na + and K + channels or optogenetic stimulation impacts the (iv) migration and/or morphogenesis of neonatal cortical pyramidal cells and interneurons (Bando et al, 2014;Bando et al, 2016;Bitzenhofer et al, 2021;De Marco Garcia et al, 2011;Hurni et al, 2017); and (v) morphogenesis of adult-born hippocampal (Piatti et al, 2011) and OB (Dahlen et al, 2011) GCs as well as (vi) survival of olfactory bulb GCs (Lin et al, 2010).…”