A mouse model of Bardet-Biedl Syndrome has impaired fear memory, which is rescued by lithium treatment

Autoři: Thomas K. Pak aff001;  Calvin S. Carter aff003;  Qihong Zhang aff003;  Sunny C. Huang aff001;  Charles Searby aff003;  Ying Hsu aff003;  Rebecca J. Taugher aff004;  Tim Vogel aff003;  Christopher C. Cychosz aff006;  Rachel Genova aff001;  Nina N. Moreira aff007;  Hanna Stevens aff002;  John A. Wemmie aff002;  Andrew A. Pieper aff009;  Kai Wang aff015;  Val C. Sheffield aff002
Působiště autorů: Medical Scientist Training Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America aff001;  Neuroscience Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America aff002;  Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America aff003;  Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America aff004;  Department of Veterans Affairs Medical Center, Iowa City, Iowa, United States of America aff005;  Department of Orthopedics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America aff006;  Department of Obstetrics and Gynecology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America aff007;  Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America aff008;  Harrington Discovery Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, United States of America aff009;  Department of Psychiatry, Case Western Reserve University, Cleveland, Ohio, United States of America aff010;  Geriatric Psychiatry, GRECC, Louis Stokes Cleveland VA Medical Center; Cleveland, Ohio, United States of America aff011;  Institute for Transformative Molecular Medicine, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America aff012;  Weill Cornell Autism Research Program, Weill Cornell Medicine of Cornell University, New York, United States of America aff013;  Department of Neuroscience, Case Western Reserve University, School of Medicine, Cleveland, Ohio, United States of America aff014;  Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, United States of America aff015
Vyšlo v časopise: A mouse model of Bardet-Biedl Syndrome has impaired fear memory, which is rescued by lithium treatment. PLoS Genet 17(4): e1009484. doi:10.1371/journal.pgen.1009484
Kategorie: Research Article
doi: 10.1371/journal.pgen.1009484


Primary cilia are microtubule-based organelles present on most cells that regulate many physiological processes, ranging from maintaining energy homeostasis to renal function. However, the role of these structures in the regulation of behavior remains unknown. To study the role of cilia in behavior, we employ mouse models of the human ciliopathy, Bardet-Biedl Syndrome (BBS). Here, we demonstrate that BBS mice have significant impairments in context fear conditioning, a form of associative learning. Moreover, we show that postnatal deletion of BBS gene function, as well as congenital deletion, specifically in the forebrain, impairs context fear conditioning. Analyses indicated that these behavioral impairments are not the result of impaired hippocampal long-term potentiation. However, our results indicate that these behavioral impairments are the result of impaired hippocampal neurogenesis. Two-week treatment with lithium chloride partially restores the proliferation of hippocampal neurons which leads to a rescue of context fear conditioning. Overall, our results identify a novel role of cilia genes in hippocampal neurogenesis and long-term context fear conditioning.

Klíčová slova:

Cilia – Fear conditioning – Genetically modified animals – Hippocampal neurogenesis – Hippocampus – Lithium – Mice – Mouse models


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