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The Journal of Neuroscience, September 12, 2007, 27(37):9951-9961; doi:10.1523/JNEUROSCI.1633-07.2007

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Development/Plasticity/Repair
Synaptic Integration of Adult-Generated Olfactory Bulb Granule Cells: Basal Axodendritic Centrifugal Input Precedes Apical Dendrodendritic Local Circuits

Mary C. Whitman¹ and Charles A. Greer^1,2

Departments of ¹Neurobiology and ¹Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520-8082

Correspondence should be addressed to Dr. Charles A. Greer, Department of Neurosurgery, Yale University School of Medicine, P.O. Box 208082, New Haven, CT 06520-8082. Email: charles.greer{at}yale.edu

The adult mammalian olfactory bulb (OB) receives a continuing influx of new interneurons. Neuroblasts from the subventricular zone (SVZ) migrate into the OB and differentiate into granule cells and periglomerular cells that are presumed to integrate into the synaptic circuits of the OB. We have used retroviral infection into the SVZ of mice to label adult-generated granule cells and follow their differentiation and integration into OB circuitry. Using synaptic markers and electron microscopy, we show new granule cells integrating into the reciprocal circuitry of the external plexiform layer (EPL), beginning at 21 d postinfection (dpi). We further show that synapses are formed earlier, beginning at 10 dpi, on the somata and basal dendrites of new cells in the granule cell layer (GCL), before dendritic elaboration in the EPL. In the EPL, elaborate dendritic arbors with spines are first evident at 14 dpi. The density of spines increases from 14 to 28 dpi, and then decreases by 56 dpi. Despite the initial appearance of dendritic spines at 14 dpi in the EPL, no expression of presynaptic or postsynaptic markers is seen until 21 dpi. These data suggest that adult-generated granule cells are first innervated by centrifugal or mitral/tufted cell axon collaterals in the GCL and that these inputs may contribute to their differentiation, maturation, and synaptic integration into the dendrodendritic local circuits found in the EPL.

Key words: neurogenesis; synaptogenesis; dendrite; spine; cholinergic; rostral migratory stream

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Received April 11, 2007; revised July 27, 2007; accepted July 30, 2007.

Correspondence should be addressed to Dr. Charles A. Greer, Department of Neurosurgery, Yale University School of Medicine, P.O. Box 208082, New Haven, CT 06520-8082. Email: charles.greer{at}yale.edu

This article has been cited by other articles:

				M. M. Moreno, C. Linster, O. Escanilla, J. Sacquet, A. Didier, and N. Mandairon Olfactory perceptual learning requires adult neurogenesis PNAS, October 20, 2009; 106(42): 17980 - 17985. [Abstract] [Full Text] [PDF]

				A. Mouret, G. Lepousez, J. Gras, M.-M. Gabellec, and P.-M. Lledo Turnover of Newborn Olfactory Bulb Neurons Optimizes Olfaction J. Neurosci., September 30, 2009; 29(39): 12302 - 12314. [Abstract] [Full Text] [PDF]

				Y. Livneh, N. Feinstein, M. Klein, and A. Mizrahi Sensory Input Enhances Synaptogenesis of Adult-Born Neurons J. Neurosci., January 7, 2009; 29(1): 86 - 97. [Abstract] [Full Text] [PDF]

				W. Kelsch, C.-W. Lin, and C. Lois Sequential development of synapses in dendritic domains during adult neurogenesis PNAS, October 28, 2008; 105(43): 16803 - 16808. [Abstract] [Full Text] [PDF]

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