Developmental, cellular, and behavioral phenotypes in a mouse model of congenital hypoplasia of the dentate gyrus
In the hippocampus, a widely accepted model posits that the dentate gyrus improves learning and memory by enhancing discrimination between inputs. To test this model, we studied conditional knockout mice in which the vast majority of dentate granule cells (DGCs) fail to develop – including nearly al...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/62766 |
| _version_ | 1797997663673647104 |
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| author | Amir Rattner Chantelle E Terrillion Claudia Jou Tina Kleven Shun Felix Hu John Williams Zhipeng Hou Manisha Aggarwal Susumu Mori Gloria Shin Loyal A Goff Menno P Witter Mikhail Pletnikov André A Fenton Jeremy Nathans |
| author_facet | Amir Rattner Chantelle E Terrillion Claudia Jou Tina Kleven Shun Felix Hu John Williams Zhipeng Hou Manisha Aggarwal Susumu Mori Gloria Shin Loyal A Goff Menno P Witter Mikhail Pletnikov André A Fenton Jeremy Nathans |
| author_sort | Amir Rattner |
| collection | DOAJ |
| description | In the hippocampus, a widely accepted model posits that the dentate gyrus improves learning and memory by enhancing discrimination between inputs. To test this model, we studied conditional knockout mice in which the vast majority of dentate granule cells (DGCs) fail to develop – including nearly all DGCs in the dorsal hippocampus – secondary to eliminating Wntless (Wls) in a subset of cortical progenitors with Gfap-Cre. Other cells in the Wlsfl/-;Gfap-Cre hippocampus were minimally affected, as determined by single nucleus RNA sequencing. CA3 pyramidal cells, the targets of DGC-derived mossy fibers, exhibited normal morphologies with a small reduction in the numbers of synaptic spines. Wlsfl/-;Gfap-Cre mice have a modest performance decrement in several complex spatial tasks, including active place avoidance. They were also modestly impaired in one simpler spatial task, finding a visible platform in the Morris water maze. These experiments support a role for DGCs in enhancing spatial learning and memory. |
| first_indexed | 2024-04-11T10:35:12Z |
| format | Article |
| id | doaj.art-efecf045371b47e199262306c5499373 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:35:12Z |
| publishDate | 2020-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-efecf045371b47e199262306c54993732022-12-22T04:29:18ZengeLife Sciences Publications LtdeLife2050-084X2020-10-01910.7554/eLife.62766Developmental, cellular, and behavioral phenotypes in a mouse model of congenital hypoplasia of the dentate gyrusAmir Rattner0https://orcid.org/0000-0001-9542-6212Chantelle E Terrillion1Claudia Jou2Tina Kleven3Shun Felix Hu4John Williams5Zhipeng Hou6Manisha Aggarwal7Susumu Mori8Gloria Shin9Loyal A Goff10https://orcid.org/0000-0003-2875-451XMenno P Witter11https://orcid.org/0000-0003-0285-1637Mikhail Pletnikov12André A Fenton13https://orcid.org/0000-0002-5063-1156Jeremy Nathans14https://orcid.org/0000-0001-8106-5460Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Physiology and Pharmacology, Robert F. Furchgott Center for Behavioral Neuroscience, State University of New York, Downstate Medical Center, Brooklyn, United StatesKavli Institute for Systems Neuroscience and Center for Neural Computation, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Physiology and Pharmacology, Robert F. Furchgott Center for Behavioral Neuroscience, State University of New York, Downstate Medical Center, Brooklyn, United StatesDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United StatesKavli Institute for Systems Neuroscience and Center for Neural Computation, Norwegian University of Science and Technology, Trondheim, NorwayDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, United StatesDepartment of Physiology and Pharmacology, Robert F. Furchgott Center for Behavioral Neuroscience, State University of New York, Downstate Medical Center, Brooklyn, United States; Center for Neural Science, New York University, New York, United States; Neuroscience Institute at the New York University Langone Medical Center, New York University, New York, United StatesDepartment of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States; Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, United StatesIn the hippocampus, a widely accepted model posits that the dentate gyrus improves learning and memory by enhancing discrimination between inputs. To test this model, we studied conditional knockout mice in which the vast majority of dentate granule cells (DGCs) fail to develop – including nearly all DGCs in the dorsal hippocampus – secondary to eliminating Wntless (Wls) in a subset of cortical progenitors with Gfap-Cre. Other cells in the Wlsfl/-;Gfap-Cre hippocampus were minimally affected, as determined by single nucleus RNA sequencing. CA3 pyramidal cells, the targets of DGC-derived mossy fibers, exhibited normal morphologies with a small reduction in the numbers of synaptic spines. Wlsfl/-;Gfap-Cre mice have a modest performance decrement in several complex spatial tasks, including active place avoidance. They were also modestly impaired in one simpler spatial task, finding a visible platform in the Morris water maze. These experiments support a role for DGCs in enhancing spatial learning and memory.https://elifesciences.org/articles/62766dentate gyrushippocampuslearningmemory |
| spellingShingle | Amir Rattner Chantelle E Terrillion Claudia Jou Tina Kleven Shun Felix Hu John Williams Zhipeng Hou Manisha Aggarwal Susumu Mori Gloria Shin Loyal A Goff Menno P Witter Mikhail Pletnikov André A Fenton Jeremy Nathans Developmental, cellular, and behavioral phenotypes in a mouse model of congenital hypoplasia of the dentate gyrus eLife dentate gyrus hippocampus learning memory |
| title | Developmental, cellular, and behavioral phenotypes in a mouse model of congenital hypoplasia of the dentate gyrus |
| title_full | Developmental, cellular, and behavioral phenotypes in a mouse model of congenital hypoplasia of the dentate gyrus |
| title_fullStr | Developmental, cellular, and behavioral phenotypes in a mouse model of congenital hypoplasia of the dentate gyrus |
| title_full_unstemmed | Developmental, cellular, and behavioral phenotypes in a mouse model of congenital hypoplasia of the dentate gyrus |
| title_short | Developmental, cellular, and behavioral phenotypes in a mouse model of congenital hypoplasia of the dentate gyrus |
| title_sort | developmental cellular and behavioral phenotypes in a mouse model of congenital hypoplasia of the dentate gyrus |
| topic | dentate gyrus hippocampus learning memory |
| url | https://elifesciences.org/articles/62766 |
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