Becoming a new neuron in the adult olfactory bulb

Abstract

New neurons are continually recruited throughout adulthood in certain regions of the adult mammalian brain. How these cells mature and integrate into preexisting functional circuits remains unknown. Here we describe the physiological properties of newborn olfactory bulb interneurons at five different stages of their maturation in adult mice. Patch-clamp recordings were obtained from tangentially and radially migrating young neurons and from neurons in three subsequent maturation stages. Tangentially migrating neurons expressed extrasynaptic GABAA receptors and then AMPA receptors, before NMDA receptors appeared in radially migrating neurons. Spontaneous synaptic activity emerged soon after migration was complete, and spiking activity was the last characteristic to be acquired. This delayed excitability is unique to cells born in the adult and may protect circuits from uncontrolled neurotransmitter release and neural network disruption. Our results show that newly born cells recruited into the olfactory bulb become neurons, and a unique sequence of events leads to their functional integration

GABA Regulates Dendritic Growth by Stabilizing Lamellipodia in Newly Generated Interneurons of the Olfactory Bulb

“…In the mammalian brain, ongoing neurogenesis maintains neuronal replacement in the olfactory bulb (OB) throughout life (Lois et al, 1996;Belluzzi et al, 2003;Carleton et al, 2003). Newly generated neurons from the subventricular zone (SVZ) migrate through the rostral migratory stream to the olfactory bulb, where they rapidly initiate dendritic growth and establish dendrodendritic contacts with mitral cells and other granule cells (AlvarezBuylla and Garcia-Verdugo, 2002;Bolteus and Bordey, 2004;Lledo and Saghatelyan, 2005).…”

“…Newly generated neurons from the subventricular zone (SVZ) migrate through the rostral migratory stream to the olfactory bulb, where they rapidly initiate dendritic growth and establish dendrodendritic contacts with mitral cells and other granule cells (AlvarezBuylla and Garcia-Verdugo, 2002;Bolteus and Bordey, 2004;Lledo and Saghatelyan, 2005). Although much has been learned about the sequential steps of neuroblast maturation in the olfactory bulb (Carleton et al, 2003), the mechanism and regulatory factors that control the initial period of dendrite formation and thus the first distinguishable event of integration of newly generated neurons, remain poorly understood. Identification of these mechanisms might be crucial for the development of strategies aimed at promoting the insertion of immature cells into damaged brain circuits.…”

“…Although GABA is the principal inhibitory neurotransmitter in the adult brain, it might in fact be excitatory in immature neurons including newborn neurons in the adult olfactory bulb (Ben-Ari, 2002;Carleton et al, 2003). Although it has been demonstrated that depolarizing GABA signaling modulates dendritic development of postnatally generated neurons (Ge et al, 2006), the mechanisms of these effects remain mostly unknown.…”

Chemical genetic approaches to probing cell death

“…A death pathway of interest that has been difficult to unravel is the one that occurs in olfactory receptor neurons (ORNs), the sensory neurons of the olfactory system. Residing in the olfactory epithelium lining the olfactory cavity within the nose, these cells, which serve to detect odors in the environment [39], are prone to death and represent one of the few neuronal populations, along with granule cells in the olfactory bulb [40] and the dentate gyrus of the hippocampus [41], that die and are continually replaced throughout adulthood [42]. Owing to this rare characteristic, along with their position in a stratified epithelium containing only one neuronal type [43], ORNs stand out as a model cell type for the study of neurodegeneration.…”

Une altération de la neurogenèse conduit à des troubles de l’olfaction dans la sclérose en plaques

“…Elles prolifèrent lentement et engendrent les cellules de précurseurs intermédiaires (type C) qui, eux, se divisent rapidement et se différencient ensuite en neuroblastes (cellules de type A). Ces derniers migrent au sein de la voie rostrale de migration (VRM) vers le bulbe olfactif où ils donnent naissance aux neurones granulaires et périglomérulaires [6]. Alors que la genèse des neurones du bulbe olfactif constitue la fonction primordiale de la ZSV dans le cerveau adulte, des études de traçage cellulaire démontrent que les cellules B sont aussi à l'origine d'une population d'oligodendrocytes dans la substance blanche périventriculaire.…”