Journal article
A mouse model of Bardet-Biedl Syndrome has impaired fear memory, which is rescued by lithium treatment
PLoS genetics, Vol.17(4), pp.e1009484-e1009484
04/2021
DOI: 10.1371/journal.pgen.1009484
PMID: 33886537
Abstract
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.
Details
- Title: Subtitle
- A mouse model of Bardet-Biedl Syndrome has impaired fear memory, which is rescued by lithium treatment
- Creators
- Thomas K Pak - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaCalvin S Carter - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaQihong Zhang - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaSunny C Huang - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaCharles Searby - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaYing Hsu - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaRebecca J Taugher - Department of Veterans Affairs Medical Center, Iowa City, Iowa, United States of AmericaTim Vogel - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaChristopher C Cychosz - Department of Orthopedics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaRachel Genova - Medical Scientist Training Program, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaNina N Moreira - Department of Obstetrics and Gynecology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaHanna Stevens - Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaJohn A Wemmie - Department of Molecular Physiology and Biophysics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaAndrew A Pieper - Department of Neuroscience, Case Western Reserve University, School of Medicine, Cleveland, Ohio, United States of AmericaKai Wang - Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, Iowa, United States of AmericaVal C Sheffield - Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America
- Resource Type
- Journal article
- Publication Details
- PLoS genetics, Vol.17(4), pp.e1009484-e1009484
- DOI
- 10.1371/journal.pgen.1009484
- PMID
- 33886537
- NLM abbreviation
- PLoS Genet
- ISSN
- 1553-7390
- eISSN
- 1553-7404
- Publisher
- United States
- Grant note
- DOI: 10.13039/100000053, name: National Eye Institute, award: EY011298; DOI: 10.13039/100000053, name: National Eye Institute, award: EY017168; DOI: 10.13039/100001024, name: Roy J. Carver Charitable Trust; DOI: 10.13039/100000053, name: National Eye Institute, award: P30 EY025580; DOI: 10.13039/501100018905, name: Brockman Foundation; name: Louis Stokes VA Medical Center resources and facilities, award: 19PABH134580006-AHA; name: Allen Initiative in Brain Health and Cognitive Impairment, award: RO1AG066707
- Language
- English
- Date published
- 04/2021
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biostatistics; Medical Genetics and Genomics; Obstetrics and Gynecology; Neuroscience and Pharmacology; Neurosurgery; Ophthalmology and Visual Sciences
- Record Identifier
- 9984066393402771
Metrics
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