Neuronal integration in the adult mouse olfactory bulb is a non-selective addition process

Abstract

Adult neurogenesis in the olfactory bulb (OB) is considered as a competition in which neurons scramble during a critical selection period for integration and survival. Moreover, newborn neurons are thought to replace pre-existing ones that die. Despite indirect evidence supporting this model, systematic in vivo observations are still scarce. We used two-photon in vivo imaging to study neuronal integration and survival. We show that loss of new neurons in the OB after arrival at terminal positions occurs only at low levels. Moreover, long-term observations showed that no substantial cell death occurred at later stages. Neuronal death was induced by standard doses of thymidine analogs, but disappeared when low doses were used. Finally, we demonstrate that the OB grows throughout life. This shows that neuronal selection during OB-neurogenesis does not occur after neurons reached stable positions. Moreover, this suggests that OB neurogenesis does not represent neuronal turnover but lifelong neuronal addition.

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

“…It was shown in the OB that olfactory training (Mouret et al, 2008) or overexpression of NaChBac (Lin et al, 2010) could increase recruitment during synaptic integration. In sharp contrast, it was recently demonstrated that in physiological condition selection during synaptic integration is nearly absent (Platel et al, 2019) pointing to a first selection step occuring before integration (Biebl et al, 2000;Platel et al, 2010). In agreement with these latter studies, our results suggest that survival of neuroblasts during radial migration is dependent on neuronal activity.…”

“…For example, increasing neuronal activity via olfactory training (Mouret et al, 2008) or by over-expression of the bacterial sodium channel NaChBac expression (Lin et al, 2010) enhance the number of newborn neurons integrated. By contrast, sensory deprivation via naris occlusion decreased the survival of newborn neurons in the OB (Saghatelyan et al, 2005;Yamaguchi and Mori, 2005;Platel et al, 2019).…”

“…Activity has also been shown to be a major regulation factor of interneuron integration in the olfactory system. Indeed, in the postnatal and adult rodent, new interneurons are produced throughout life (Lois and Alvarez-Buylla, 1994) and permanently added to the preexisting circuitry of the olfactory bulb (OB) (Platel et al, 2019). In this system neural stem cells localized in the V-SVZ along lateral ventricles generate neuronal precursors that migrate tangentially via the rostral migratory stream (RMS) into the core of the OB.…”

Enhanced endogenous activity predicts elimination of adult-born neurons in the mouse olfactory bulb

“…Thousands of ABCs migrate into the OB every day but many of them are thought to be eliminated by programmed cell death [17][18][19][20][21][22] (but see ref. 23). According to data obtained in bromodeoxyuridine (BrdU) incorporation experiments, elimination of ABCs mainly happens between 15 and 45 days after birth [20][21][22] .…”

Regulatory interactions between Vax1, Pax6, and miR-7 regionalize the lateral Ventricular-Subventricular Zone during post-natal Olfactory Bulb neurogenesis in mice

“…In the postnatal and adult rodent forebrain, new interneuron precursors are continuously generated by neural stem cell populations along the walls of the lateral ventricles. After their amplification in the subventricular zone (SVZ) and long-distance migration via the rostral migratory stream (RMS), they are added to the preexisting circuitry of the olfactory bulb (OB) Whitman and Greer, 2009;Platel et al, 2019).…”