title: A Transgenic Rat for Specifically Inhibiting Adult Neurogenesis.
abstract: The growth of research on adult neurogenesis and the development of new models and tools have greatly advanced our understanding of the function of newborn neurons in recent years. However, there are still significant limitations in the ability to identify the functions of adult neurogenesis in available models. Here we report a transgenic rat (TK rat) that expresses herpes simplex virus thymidine kinase in GFAP+ cells. Upon treating TK rats with the antiviral drug valganciclovir, granule cell neurogenesis can be completely inhibited in adulthood, in both the hippocampus and olfactory bulb. Interestingly, neurogenesis in the glomerular and external plexiform layers of the olfactory bulb was only partially inhibited, suggesting that some adult-born neurons in these regions derive from a distinct precursor population that does not express GFAP. Within the hippocampus, blockade of neurogenesis was rapid and nearly complete within 1 week of starting treatment. Preliminary behavioral analyses indicate that general anxiety levels and patterns of exploration are generally unaffected in neurogenesis-deficient rats. However, neurogenesis-deficient TK rats showed reduced sucrose preference, suggesting deficits in reward-related behaviors. We expect that TK rats will facilitate structural, physiological, and behavioral studies that complement those possible in existing models, broadly enhancing understanding of the function of adult neurogenesis.
authors.affiliation: Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892; Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Jason S
authors.identifier: 0000-0002-5509-0272
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: Laura
authors.initials: L
authors.lastname: Grigereit
authors.affiliation: Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Alexandra
authors.identifier: 0000-0001-9775-2855
authors.initials: A
authors.lastname: Russo
authors.affiliation: Department of Psychology, Djavad Mowafaghian Centre for Brain Health, University of British Columbia , Vancouver, BC, V6T 1Z4, Canada.
authors.forename: Désirée R
authors.identifier: 0000-0001-9953-8270
authors.initials: DR
authors.lastname: Seib
authors.affiliation: Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Michelle
authors.identifier: 0000-0002-8857-6105
authors.initials: M
authors.lastname: Brewer
authors.affiliation: Transgenic Core Facility, National Institute of Mental Health, National Institutes of Health , Bethesda, Maryland 20892, and.
authors.forename: James
authors.initials: J
authors.lastname: Pickel
authors.affiliation: Section on Neuroplasticity, National Institute of Mental Health, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Heather A
authors.identifier: 0000-0002-3245-5777
authors.initials: HA
authors.lastname: Cameron
mesh_terms: D053687:Adult Stem Cells / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D060906:Coxa Valga; D019422:Dietary Sucrose; D005106:Exploratory Behavior / Q000502:physiology; D005518:Food Preferences / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000254:growth & development / Q000473:pathology / Q000502:physiology; D006801:Humans; D008297:Male; D023421:Models, Animal; D055495:Neurogenesis / Q000502:physiology*; D009830:Olfactory Bulb / Q000254:growth & development / Q000473:pathology / Q000502:physiology; D055647:Rats, Transgenic; D012201:Reward; D018139:Simplexvirus; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D019422:Dietary Sucrose; D005904:Glial Fibrillary Acidic Protein; D014764:Viral Proteins; D013937:Thymidine Kinase
keywords: adult neurogenesis; hippocampus; olfactory bulb; plasticity