title: Adult neurogenesis is necessary to refine and maintain circuit specificity.
abstract: The circuitry of the olfactory bulb contains a precise anatomical map that links isofunctional regions within each olfactory bulb. This intrabulbar map forms perinatally and undergoes activity-dependent refinement during the first postnatal weeks. Although this map retains its plasticity throughout adulthood, its organization is remarkably stable despite the addition of millions of new neurons to this circuit. Here we show that the continuous supply of new neuroblasts from the subventricular zone is necessary for both the restoration and maintenance of this precise central circuit. Using pharmacogenetic methods to conditionally ablate adult neurogenesis in transgenic mice, we find that the influx of neuroblasts is required for recovery of intrabulbar map precision after disruption due to sensory block. We further demonstrate that eliminating adult-born interneurons in naive animals leads to an expansion of tufted cell axons that is identical to the changes caused by sensory block, thus revealing an essential role for new neurons in circuit maintenance under baseline conditions. These findings show, for the first time, that inhibiting adult neurogenesis alters the circuitry of projection neurons in brain regions that receive new interneurons and points to a critical role for adult-born neurons in stabilizing a brain circuit that exhibits high levels of plasticity.
authors.affiliation: Developmental Neural Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, and.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Cummings
authors.affiliation: Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Snyder
authors.affiliation: Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Michelle
authors.identifier: http://orcid.org/0000-0002-8857-6105
authors.initials: M
authors.lastname: Brewer
authors.affiliation: Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Cameron
authors.affiliation: Developmental Neural Plasticity Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, and belluscl@ninds.nih.gov.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Belluscio
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein; D020547:Lateral Ventricles / Q000254:growth & development / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D064231:Nestin / Q000235:genetics / Q000502:physiology; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis / Q000502:physiology*; D009830:Olfactory Bulb / Q000254:growth & development / Q000502:physiology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; C528900:glial fibrillary astrocytic protein, mouse
keywords: interneuron; intrabulbar map; neurogenesis; olfactory deprivation; rostral migratory stream; subventricular zone