Abstract
Adult-born neurons (ABNs) are added to the olfactory bulb (OB) throughout life in rodents. While many factors have been identified as regulating the survival and integration of ABNs into existing circuitry, the understanding of how these factors affect ABN morphology and connectivity is limited. Here we compare how cell intrinsic [small interfering RNA (siRNA) knock-down of voltage gated sodium channels NaV1.1–1.3] and circuit level (naris occlusion) reductions in activity affect ABN morphology during integration into the OB. We found that both manipulations reduce the number of dendritic spines (and thus likely the number of reciprocal synaptic connections) formed with the surrounding circuitry and inhibited dendritic ramification of ABNs. Further, we identified regions of ABN apical dendrites where the largest and most significant decreases occur following siRNA knock-down or naris occlusion. In siRNA knock-down cells, reduction of spines is observed in proximal regions of the apical dendrite. This suggests that distal regions of the dendrite may remain active independent of NaV1.1–1.3 channel expression, perhaps facilitated by activation of T-type calcium channels and NMDA receptors. By contrast, circuit level reduction of activity by naris occlusion resulted in a global depression of spine number. Together, these results indicate that ABNs retain the ability to develop their typical overall morphological features regardless of experienced activity, and activity modulates the number and location of formed connections.
Highlights
Adult neurogenesis contributes adult-born neurons (ABNs) to the mouse olfactory bulb (OB) throughout life (Altman, 1969)
EGFP-encoding lentivirus labels adult-born granule cells To visualize ABNs in the OB, we injected lentiviruses encoding EGFP into the subventricular zone (SVZ) of adult mice. This virus infected and labeled neural progenitors, which migrate along the rostral migratory stream (RMS) to the OB and integrate as inhibitory granule cells
To measure the effects of manipulating activity on ABN morphology, we considered two groups of animals (Figures 1C,D)
Summary
Adult neurogenesis contributes adult-born neurons (ABNs) to the mouse olfactory bulb (OB) throughout life (Altman, 1969). A small fraction of these ABNs mature to become periglomerular neurons, but the majority of ABNs become local circuit interneurons morphologically similar to neonatal granule cells (Carleton et al, 2003; Saghatelyan et al, 2005; Ninkovic et al, 2007). Following their migration, many factors influence the survival of ABNs in the olfactory system (Alonso et al, 2006; Lazarini and Lledo, 2010). Information about these connections will, in turn, indicate how much input ABNs are receiving from the existing network, while revealing the influence these new cells may have on network activity
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