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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.

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Figure 1: Newborn neurons are functionally integrated into the adult olfactory bulb.
Figure 2: Functional properties of class-1 and class-2 newborn granule cells.
Figure 3: Functional properties of class-3 and class-4 newborn granule cells.
Figure 4: Functional properties of class-5 newborn granule cells.
Figure 5: Summary graphs of changes in intrinsic membrane properties during neuronal maturation.
Figure 6: Delayed maturation of excitability is a feature of adult neurogenesis.
Figure 7: Changes in synaptic activity during neuronal maturation.
Figure 8: Two populations of newborn granule cells were distinguished according to their location in the GC layer.

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Acknowledgements

This work was supported by the Pasteur Institute, the Annette Gruner-Schlumberger Foundation, the CNRS, the Fondation pour la Recherche Médicale, a grant from the French Ministry of Research and Education (ACI Biologie du Développement et Physiologie Intégrative 2000) and by a National Institutes of Health grant HD32116. We thank E. Perret and M.M. Gabellec for technical help with the confocal microscope and immunocytochemistry, respectively. We also thank A. Saghatelyan, M. Davenne and I. Manns for critical reading of the manuscript.

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Correspondence to Pierre-Marie Lledo.

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Supplementary information

Supplementary Fig. 1.

Summary Graphs of the sIPSC Kinetics. (a) IPSC rise times obtained for the different neuronal classes are presented as cumulative plots (see Supplementary Table for the number of tested neurons). There is no statistical difference between values obtained from cells belonging to different classes (K-S test: the numbers in parenthesis indicate the classes), which indicates that the location of the inhibitory contacts remains the same throughout maturation. (b) Graph showing no relation between the rise time and the decay time of average IPSCs. Each dot represents an individual cell recorded from one of the different classes, as depicted by the color code (green, red and black for classes 3, 4 and 5 respectively, n = 73). Note the absence of correlation between the two parameters (R2, square regression index) demonstrating that the decay time variability does not result from dendritic filtering. (GIF 18 kb)

Supplementary Table 1 (PDF 18 kb)

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Carleton, A., Petreanu, L., Lansford, R. et al. Becoming a new neuron in the adult olfactory bulb. Nat Neurosci 6, 507–518 (2003). https://doi.org/10.1038/nn1048

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