Why Some Mice Are Smarter than Others: The Impact of Bone Morphogenetic Protein Signaling on Cognition

• Published in: eNeuro Vol. 10; no. 1; p. ENEURO.0213-22.2022
• Main Authors: Bonds, Jacqueline A, Tunc-Ozcan, Elif, Dunlop, Sara R, Rawat, Radhika, Peng, Chian-Yu, Kessler, John A
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 01-01-2023
• Subjects: Aging; Animals; Bone Morphogenetic Proteins - metabolism; Bone Morphogenetic Proteins - pharmacology; Cognition; Hippocampus - metabolism; Mice; New Research; novel object recognition; cognition; bone morphogenetic protein; noggin
• ISSN: 2373-2822; 2373-2822
• DOI: 10.1523/ENEURO.0213-22.2022

Inbred mice (C57Bl/6) display wide variability in performance on hippocampal-dependent cognitive tasks. Examination of microdissected dentate gyrus (DG) after cognitive testing showed a highly significant negative correlation between levels of bone morphogenetic protein (BMP) signaling and recognition memory. Cognitive performance decline during the aging process, and the degree of cognitive decline is strongly correlated with aging-related increases in BMP signaling. Further, cognitive performance was impaired when the BMP inhibitor, noggin, was knocked down in the DG. Infusion of noggin into the lateral ventricles enhanced DG-dependent cognition while BMP4 infusion led to significant impairments. Embryonic overexpression of noggin resulted in lifelong enhancement of recognition and spatial memory while overexpression of BMP4 resulted in lifelong impairment, substantiating the importance of differences in BMP signaling in wild-type mice. These findings indicate that performance in DG-dependent cognitive tasks is largely determined by differences in levels BMP signaling in the dentate gyrus.