For morphometric analyses we used quantitative, unbiased stereological procedures in combination with two well-characterized, transgenically targeted mouse models for either lineage analysis or near complete and permanent ablation of PNN while leaving embryonic neurogenesis intact, in order to define the temporal dynamics and precise contribution of PNN to the adult compliment of OB and DG granule neurons during the juvenile period.įunctionally, PNN has been implicated in odor-based learning in the OB ( Lazarini and Lledo, 2011), and in the DG it has been implicated in learning and memory processes, as well as neuropsychiatric and neurological disorders ( Deng et al., 2010 Sahay et al., 2011b). In this study, we evaluated the structural and behavioral roles of PNN using quantitative morphometry and behavioral evaluations in combination with a transgenic loss of function model. The more inclusive term of postnatal neurogenesis (PNN) is a far more accurate description of field of adult neurogenesis as a whole and will be the primary term used here. A precise definition of the distinction between juvenile and adult neurogenesis is, therefore, needed in order to determine their potentially different structural and functional roles (e.g., Wei et al., 2011). Furthermore, the term “adult” neurogenesis has been applied across studies with substantial differences in the age of the animal. Now classical studies reported that juvenile neurogenesis adds to the final adult complement of granule neurons in OB and DG ( Altman and Das, 1965 Bayer et al., 1982), but neither the total numbers of granule neurons added, nor the temporal dynamics of that addition during juvenile development, have been defined. Although neurogenesis in the adult brain has been under intense investigation for some time, neurogenesis during the juvenile period has received far less attention. These new neurons integrate with embryonically generated neurons and make important, though incompletely understood, functional contributions to cognition and behavior ( Deng et al., 2010 Lazarini and Lledo, 2011). New neurons are continuously generated in the juvenile and adult brain in two major regions, the subgranular zone (SGZ), which contributes neurons to the dentate gyrus (DG) of the hippocampus, and the sub-ventricular zone (SVZ), which contributes neurons to the olfactory bulb (OB). Thus, juvenile neurogenesis adds substantively to the total numbers of granule neurons in OB and DG during periods of critical juvenile behavioral development, including weaning, early social interactions and sexual maturation, and plays a sex-dependent role in fear memories. We also observed a reduced reliance on olfactory cues, consistent with a role for OB PNN in the efficient processing of olfactory information. Contextual discrimination between two highly similar contexts was enhanced suggesting either enhanced contextual pattern separation or impaired temporal integration. Standard contextual fear conditioning was intact, however, pre-exposure dependent contextual fear was impaired suggesting a specific role for PNN in incidental contextual learning. We observed normal hippocampus-independent delay fear conditioning, but excessive generalization of fear to a novel auditory stimulus, which is consistent with a role for PNN in psychopathology. Behavioral analysis in our conditional cell ablation mouse model showed that complete loss of PNN throughout both the juvenile and young adult period produced a specific set of sex-dependent cognitive changes. These findings indicate that the overwhelming majority of net postnatal neuronal addition in these regions occurs during the juvenile period and that adult neurogenesis contributes primarily to replacement of granule cells in both regions. By using transgenic mouse models for cell lineage tracing and conditional cell ablation, we found that juvenile neurogenesis gradually increased the total number of granule neurons by approximately 40% in OB, and by 25% in DG, between 2 weeks and 2 months of age, and that total numbers remained stable thereafter. Postnatal neurogenesis (PNN) contributes neurons to olfactory bulb (OB) and dentate gyrus (DG) throughout juvenile development, but the quantitative amount, temporal dynamics and functional roles of this contribution have not been defined. 3Department of Human Genetics, University of California Los Angeles, Los Angeles, CA, USA.2Department of Neurobiology, University of California Los Angeles, Los Angeles, CA, USA.1Departments of Psychology and Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, USA.Denise Garcia 2† Guoping Fan 3† Tetsuya Imura 2† Michael V. Cushman 1* †‡ Jose Maldonado 2†‡ Eunice E.
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