Developmental, cellular, and behavioral phenotypes in a mouse model of congenital hypoplasia of the dentate gyrus

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere62766
Pages (from-to)1-30
Number of pages30
JournaleLife
Volume9
DOIs
StatePublished - Oct 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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