Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States
Chantelle E Terrillion
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, United States
Claudia Jou
Department of Physiology and Pharmacology, Robert F. Furchgott Center for Behavioral Neuroscience, State University of New York, Downstate Medical Center, Brooklyn, United States
Tina Kleven
Kavli Institute for Systems Neuroscience and Center for Neural Computation, Norwegian University of Science and Technology, Trondheim, Norway
Shun Felix Hu
Department of Physiology and Pharmacology, Robert F. Furchgott Center for Behavioral Neuroscience, State University of New York, Downstate Medical Center, Brooklyn, United States
John Williams
Department 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
Zhipeng Hou
Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, United States
Manisha Aggarwal
Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, United States
Susumu Mori
Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, United States
Gloria Shin
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States; Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, United States
Department 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 States
Department 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 States
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.
