Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model
The function of adult neurogenesis in the rodent brain remains unclear. Ablation of adult born neurons has yielded conflicting results about emotional and cognitive impairments. One hypothesis is that adult neurogenesis in the hippocampus enables spatial pattern separation, allowing animals to disti...
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| creator | Groves, James O Leslie, Isla Huang, Guo-Jen McHugh, Stephen B Taylor, Amy Mott, Richard Munafò, Marcus Bannerman, David M Flint, Jonathan |
| description | The function of adult neurogenesis in the rodent brain remains unclear. Ablation of adult born neurons has yielded conflicting results about emotional and cognitive impairments. One hypothesis is that adult neurogenesis in the hippocampus enables spatial pattern separation, allowing animals to distinguish between similar stimuli. We investigated whether spatial pattern separation and other putative hippocampal functions of adult neurogenesis were altered in a novel genetic model of neurogenesis ablation in the rat. In rats engineered to express thymidine kinase (TK) from a promoter of the rat glial fibrillary acidic protein (GFAP), ganciclovir treatment reduced new neurons by 98%. GFAP-TK rats showed no significant difference from controls in spatial pattern separation on the radial maze, spatial learning in the water maze, contextual or cued fear conditioning. Meta-analysis of all published studies found no significant effects for ablation of adult neurogenesis on spatial memory, cue conditioning or ethological measures of anxiety. An effect on contextual freezing was significant at a threshold of 5% (P = 0.04), but not at a threshold corrected for multiple testing. The meta-analysis revealed remarkably high levels of heterogeneity among studies of hippocampal function. The source of this heterogeneity remains unclear and poses a challenge for studies of the function of adult neurogenesis. |
| doi_str_mv | 10.1371/journal.pgen.1003718 |
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Ablation of adult born neurons has yielded conflicting results about emotional and cognitive impairments. One hypothesis is that adult neurogenesis in the hippocampus enables spatial pattern separation, allowing animals to distinguish between similar stimuli. We investigated whether spatial pattern separation and other putative hippocampal functions of adult neurogenesis were altered in a novel genetic model of neurogenesis ablation in the rat. In rats engineered to express thymidine kinase (TK) from a promoter of the rat glial fibrillary acidic protein (GFAP), ganciclovir treatment reduced new neurons by 98%. GFAP-TK rats showed no significant difference from controls in spatial pattern separation on the radial maze, spatial learning in the water maze, contextual or cued fear conditioning. Meta-analysis of all published studies found no significant effects for ablation of adult neurogenesis on spatial memory, cue conditioning or ethological measures of anxiety. An effect on contextual freezing was significant at a threshold of 5% (P = 0.04), but not at a threshold corrected for multiple testing. The meta-analysis revealed remarkably high levels of heterogeneity among studies of hippocampal function. The source of this heterogeneity remains unclear and poses a challenge for studies of the function of adult neurogenesis.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1003718</identifier><identifier>PMID: 24039591</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animal memory ; Animals ; Anxiety - physiopathology ; Behavior ; Cell growth ; Cognitive Dysfunction - genetics ; Cognitive Dysfunction - pathology ; Conditioning, Psychological ; Fear - physiology ; Glial Fibrillary Acidic Protein - genetics ; Glial Fibrillary Acidic Protein - metabolism ; Hippocampus - metabolism ; Hippocampus - physiology ; Maze Learning - physiology ; Memory - physiology ; Meta-analysis ; Neurogenesis ; Neurogenesis - genetics ; Neurons - metabolism ; Pharmacogenetics ; Rats ; Rodents ; Spatial behavior in animals ; Studies ; Thymidine Kinase - genetics ; Thymidine Kinase - metabolism</subject><ispartof>PLoS genetics, 2013-09, Vol.9 (9), p.e1003718-e1003718</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Groves et al 2013 Groves et al</rights><rights>2013 Groves et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited: Groves JO, Leslie I, Huang G-J, McHugh SB, Taylor A, et al. (2013) Ablating Adult Neurogenesis in the Rat Has No Effect on Spatial Processing: Evidence from a Novel Pharmacogenetic Model. 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Ablation of adult born neurons has yielded conflicting results about emotional and cognitive impairments. One hypothesis is that adult neurogenesis in the hippocampus enables spatial pattern separation, allowing animals to distinguish between similar stimuli. We investigated whether spatial pattern separation and other putative hippocampal functions of adult neurogenesis were altered in a novel genetic model of neurogenesis ablation in the rat. In rats engineered to express thymidine kinase (TK) from a promoter of the rat glial fibrillary acidic protein (GFAP), ganciclovir treatment reduced new neurons by 98%. GFAP-TK rats showed no significant difference from controls in spatial pattern separation on the radial maze, spatial learning in the water maze, contextual or cued fear conditioning. Meta-analysis of all published studies found no significant effects for ablation of adult neurogenesis on spatial memory, cue conditioning or ethological measures of anxiety. An effect on contextual freezing was significant at a threshold of 5% (P = 0.04), but not at a threshold corrected for multiple testing. The meta-analysis revealed remarkably high levels of heterogeneity among studies of hippocampal function. The source of this heterogeneity remains unclear and poses a challenge for studies of the function of adult neurogenesis.</description><subject>Animal memory</subject><subject>Animals</subject><subject>Anxiety - physiopathology</subject><subject>Behavior</subject><subject>Cell growth</subject><subject>Cognitive Dysfunction - genetics</subject><subject>Cognitive Dysfunction - pathology</subject><subject>Conditioning, Psychological</subject><subject>Fear - physiology</subject><subject>Glial Fibrillary Acidic Protein - genetics</subject><subject>Glial Fibrillary Acidic Protein - metabolism</subject><subject>Hippocampus - metabolism</subject><subject>Hippocampus - physiology</subject><subject>Maze Learning - physiology</subject><subject>Memory - physiology</subject><subject>Meta-analysis</subject><subject>Neurogenesis</subject><subject>Neurogenesis - genetics</subject><subject>Neurons - metabolism</subject><subject>Pharmacogenetics</subject><subject>Rats</subject><subject>Rodents</subject><subject>Spatial behavior in animals</subject><subject>Studies</subject><subject>Thymidine Kinase - genetics</subject><subject>Thymidine Kinase - metabolism</subject><issn>1553-7404</issn><issn>1553-7390</issn><issn>1553-7404</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNqVk12L1DAUhoso7rr6D0QDgujFjE2TTlMvhGHxY2Bxwa_bkCYnbZY0mU3SUf-9mZ3ZZQa8UHqRcvK8Tw4Jpyie4nKOSYPfXPkpOGHn6x7cHJdlrrF7xSmuazJraEnvH_yfFI9ivMpMzdrmYXFS0ZK0dYtPi5_LzopkXI-EmmxCDqbgsxGiicg4lAZAQSQ0iIicR6A1yIS8Q3GdY8KidfASYsyGtwg2RoGTgHTwIxI5sIFMDCKMQt5Yk5Fo9Ars4-KBFjbCk_16Vnz_8P7b-afZxeXH1fnyYiYXLUszscCqqqlSgqhKM80wbqTqtG5llatdxQADoQ1TpCMV7pRsGpCqrXXJWkUJOSue77xr6yPf31nkmNKKLkhdlZlY7QjlxRVfBzOK8Jt7YfhNwYeei5D7tsCVrtoOl4wwSShRlDGpgTQ1bTHO3eDserc_bepGUBJcCsIeSY93nBl47zecNAuK663g1V4Q_PUEMfHRRAnWCgd-2vZNSLVoSFln9MUO7UVuzTjts1Fucb4klFV4weiWmv-Fyp-C0UjvQJtcPwq8PgpkJsGv1IspRr76-uU_2M__zl7-OGZfHrADCJuG6O2UjHfxGKQ7UAYfYwB9d9W45NspuX1xvp0Svp-SHHt2-Ex3oduxIH8ALsYOAw</recordid><startdate>20130901</startdate><enddate>20130901</enddate><creator>Groves, James O</creator><creator>Leslie, Isla</creator><creator>Huang, Guo-Jen</creator><creator>McHugh, Stephen B</creator><creator>Taylor, Amy</creator><creator>Mott, Richard</creator><creator>Munafò, Marcus</creator><creator>Bannerman, David M</creator><creator>Flint, Jonathan</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20130901</creationdate><title>Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model</title><author>Groves, James O ; 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Ablation of adult born neurons has yielded conflicting results about emotional and cognitive impairments. One hypothesis is that adult neurogenesis in the hippocampus enables spatial pattern separation, allowing animals to distinguish between similar stimuli. We investigated whether spatial pattern separation and other putative hippocampal functions of adult neurogenesis were altered in a novel genetic model of neurogenesis ablation in the rat. In rats engineered to express thymidine kinase (TK) from a promoter of the rat glial fibrillary acidic protein (GFAP), ganciclovir treatment reduced new neurons by 98%. GFAP-TK rats showed no significant difference from controls in spatial pattern separation on the radial maze, spatial learning in the water maze, contextual or cued fear conditioning. Meta-analysis of all published studies found no significant effects for ablation of adult neurogenesis on spatial memory, cue conditioning or ethological measures of anxiety. An effect on contextual freezing was significant at a threshold of 5% (P = 0.04), but not at a threshold corrected for multiple testing. The meta-analysis revealed remarkably high levels of heterogeneity among studies of hippocampal function. The source of this heterogeneity remains unclear and poses a challenge for studies of the function of adult neurogenesis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24039591</pmid><doi>10.1371/journal.pgen.1003718</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Animal memory Animals Anxiety - physiopathology Behavior Cell growth Cognitive Dysfunction - genetics Cognitive Dysfunction - pathology Conditioning, Psychological Fear - physiology Glial Fibrillary Acidic Protein - genetics Glial Fibrillary Acidic Protein - metabolism Hippocampus - metabolism Hippocampus - physiology Maze Learning - physiology Memory - physiology Meta-analysis Neurogenesis Neurogenesis - genetics Neurons - metabolism Pharmacogenetics Rats Rodents Spatial behavior in animals Studies Thymidine Kinase - genetics Thymidine Kinase - metabolism |
| title | Ablating adult neurogenesis in the rat has no effect on spatial processing: evidence from a novel pharmacogenetic model |
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