{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T21:27:21Z","timestamp":1782422841117,"version":"3.54.5"},"reference-count":93,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY011298"],"award-info":[{"award-number":["EY011298"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY017168"],"award-info":[{"award-number":["EY017168"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001024","name":"Roy J. Carver Charitable Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30 EY025580"],"award-info":[{"award-number":["P30 EY025580"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018905","name":"Brockman Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018905","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Louis Stokes VA Medical Center resources and facilities","award":["19PABH134580006-AHA"],"award-info":[{"award-number":["19PABH134580006-AHA"]}]},{"name":"Allen Initiative in Brain Health and Cognitive Impairment","award":["RO1AG066707"],"award-info":[{"award-number":["RO1AG066707"]}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1371\/journal.pgen.1009484","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T13:37:35Z","timestamp":1619098655000},"page":"e1009484","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["A mouse model of Bardet-Biedl Syndrome has impaired fear memory, which is rescued by lithium treatment"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2716-1210","authenticated-orcid":true,"given":"Thomas K.","family":"Pak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8275-8330","authenticated-orcid":true,"given":"Calvin S.","family":"Carter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3458-8677","authenticated-orcid":true,"given":"Sunny C.","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8108-8782","authenticated-orcid":true,"given":"Charles","family":"Searby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0396-9680","authenticated-orcid":true,"given":"Ying","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6710-984X","authenticated-orcid":true,"given":"Rebecca J.","family":"Taugher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4371-122X","authenticated-orcid":true,"given":"Tim","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher C.","family":"Cychosz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Genova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6476-4518","authenticated-orcid":true,"given":"Nina N.","family":"Moreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3906-0786","authenticated-orcid":true,"given":"Hanna","family":"Stevens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Wemmie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6299-6577","authenticated-orcid":true,"given":"Andrew A.","family":"Pieper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3229-9866","authenticated-orcid":true,"given":"Kai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6282-0835","authenticated-orcid":true,"given":"Val C.","family":"Sheffield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"issue":"11","key":"pgen.1009484.ref001","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1523\/JNEUROSCI.0599-17.2018","article-title":"Rescue of Learning and Memory Deficits in the Human Nonsyndromic Intellectual Disability Cereblon Knock-Out Mouse Model by Targeting the AMP-Activated Protein Kinase\u2013mTORC1 Translational Pathway","volume":"38","author":"CC Bavley","year":"2018","journal-title":"The Journal of Neuroscience"},{"issue":"2","key":"pgen.1009484.ref002","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.ridd.2010.12.018","article-title":"Prevalence of intellectual disability: A meta-analysis of population-based studies.","volume":"32","author":"PK Maulik","year":"2011","journal-title":"Research in Developmental Disabilities"},{"issue":"12","key":"pgen.1009484.ref003","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.2337\/db13-0880","article-title":"Glucose-6-phosphate-mediated activation of liver glycogen synthase plays a key role in hepatic glycogen synthesis","volume":"62","author":"A von Wilamowitz-Moellendorff","year":"2013","journal-title":"Diabetes"},{"issue":"3","key":"pgen.1009484.ref004","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/ana.24002","article-title":"New innovations: therapeutic opportunities for intellectual disabilities","volume":"74","author":"JD Picker","year":"2013","journal-title":"Annals of neurology"},{"issue":"Suppl 1","key":"pgen.1009484.ref005","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1590\/S1807-59322011001300007","article-title":"Animal models of intellectual disability: towards a translational approach","volume":"66","author":"CA Scorza","year":"2011","journal-title":"Clinics (Sao Paulo, Brazil)."},{"issue":"1","key":"pgen.1009484.ref006","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.cmet.2014.11.019","article-title":"Metabolic regulation and energy homeostasis through the primary Cilium","volume":"21","author":"EC Oh","year":"2015","journal-title":"Cell metabolism"},{"issue":"218","key":"pgen.1009484.ref007","volume":"13","author":"SM Park","year":"2019","journal-title":"Roles of Primary Cilia in the Developing Brain. Frontiers in Cellular Neuroscience"},{"issue":"6","key":"pgen.1009484.ref008","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1136\/jmg.36.6.437","article-title":"New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey","volume":"36","author":"PL Beales","year":"1999","journal-title":"Journal of medical genetics"},{"issue":"1","key":"pgen.1009484.ref009","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/ejhg.2012.115","article-title":"Bardet-Biedl syndrome. European journal of human genetics","volume":"21","author":"E Forsythe","year":"2013","journal-title":"EJHG"},{"key":"pgen.1009484.ref010","author":"V Sheffield","year":"2016","journal-title":"Epstein\u2019s Inborn Errors of Development: The Molecular Basis of Clinical Disorders of Morphogenesis: Oxford University Press"},{"issue":"6","key":"pgen.1009484.ref011","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/j.cell.2007.03.053","article-title":"A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis","volume":"129","author":"MV Nachury","year":"2007","journal-title":"Cell"},{"issue":"6","key":"pgen.1009484.ref012","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.devcel.2008.11.001","article-title":"A BBSome subunit links ciliogenesis, microtubule stability, and acetylation","volume":"15","author":"AV Loktev","year":"2008","journal-title":"Dev Cell"},{"issue":"4","key":"pgen.1009484.ref013","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/ng935","article-title":"Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome","volume":"31","author":"K Mykytyn","year":"2002","journal-title":"Nature genetics"},{"issue":"9","key":"pgen.1009484.ref014","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1093\/hmg\/dds004","article-title":"BBS proteins interact genetically with the IFT pathway to influence SHH-related phenotypes","volume":"21","author":"Q Zhang","year":"2012","journal-title":"Human Molecular Genetics"},{"issue":"5","key":"pgen.1009484.ref015","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1016\/j.celrep.2013.11.011","article-title":"Neuropeptide Y Family Receptors Traffic via the Bardet-Biedl Syndrome Pathway to Signal in Neuronal Primary Cilia.","volume":"5","author":"V Loktev Alexander","year":"2013","journal-title":"Cell Reports"},{"key":"pgen.1009484.ref016","first-page":"105","article-title":"Bardet-Biedl syndrome proteins are required for the localization of G protein-coupled receptors to primary cilia","author":"NF Berbari","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"issue":"17","key":"pgen.1009484.ref017","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1007\/s00018-010-0603-4","article-title":"Dopamine receptor 1 localizes to neuronal cilia in a dynamic process that requires the Bardet-Biedl syndrome proteins. Cellular and molecular life sciences","volume":"68","author":"JS Domire","year":"2011","journal-title":"CMLS"},{"issue":"5","key":"pgen.1009484.ref018","doi-asserted-by":"crossref","first-page":"e98687","DOI":"10.1371\/journal.pone.0098687","article-title":"BBS4 Is Necessary for Ciliary Localization of TrkB Receptor and Activation by BDNF.","volume":"9","author":"CC Leitch","year":"2014","journal-title":"PLOS ONE"},{"issue":"4","key":"pgen.1009484.ref019","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1073\/pnas.0910268107","article-title":"BBS6, BBS10, and BBS12 form a complex with CCT\/TRiC family chaperonins and mediate BBSome assembly","volume":"107","author":"S Seo","year":"2010","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"51","key":"pgen.1009484.ref020","doi-asserted-by":"crossref","first-page":"20678","DOI":"10.1073\/pnas.1113220108","article-title":"knockout mouse model reveals common BBS-associated phenotypes and Bbs3 unique phenotypes","volume":"108","author":"Q Zhang","year":"2011","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"9","key":"pgen.1009484.ref021","article-title":"Keeping an Eye on Bardet-Biedl Syndrome: A Comprehensive Review of the Role of Bardet-Biedl Syndrome Genes in the Eye","volume":"5","author":"K Weihbrecht","year":"2017","journal-title":"Medical research archives"},{"issue":"49","key":"pgen.1009484.ref022","doi-asserted-by":"crossref","first-page":"19422","DOI":"10.1073\/pnas.0708571104","article-title":"A knockin mouse model of the Bardet-Biedl syndrome 1 M390R mutation has cilia defects, ventriculomegaly, retinopathy, and obesity","volume":"104","author":"RE Davis","year":"2007","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"1","key":"pgen.1009484.ref023","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ajmg.a.33773","article-title":"Neocortical and hippocampal volume loss in a human ciliopathy: A quantitative MRI study in Bardet\u2013Biedl syndrome","volume":"155","author":"K Baker","year":"2011","journal-title":"American Journal of Medical Genetics Part A"},{"key":"pgen.1009484.ref024","author":"JN Crawley","year":"2006"},{"issue":"11","key":"pgen.1009484.ref025","first-page":"5369","article-title":"Pharmacological Modulation of AMPAR Rescues Intellectual Disability-Like Phenotype in Tm4sf2-\/y Mice.","volume":"27","author":"L Murru","year":"2017","journal-title":"Cerebral cortex (New York, NY: 1991)."},{"issue":"2","key":"pgen.1009484.ref026","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.bbr.2011.09.039","article-title":"Behavioral characterization of cereblon forebrain-specific conditional null mice: A model for human non-syndromic intellectual disability.","volume":"226","author":"AM Rajadhyaksha","year":"2012","journal-title":"Behavioural brain research"},{"issue":"16","key":"pgen.1009484.ref027","doi-asserted-by":"crossref","first-page":"6423","DOI":"10.1523\/JNEUROSCI.23-16-06423.2003","article-title":"Individual Differences in the Expression of a \u201cGeneral\u201d Learning Ability in Mice.","volume":"23","author":"LD Matzel","year":"2003","journal-title":"The Journal of Neuroscience"},{"issue":"2","key":"pgen.1009484.ref028","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1037\/0735-7044.106.2.274","article-title":"Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning","volume":"106","author":"RG Phillips","year":"1992","journal-title":"Behavioral neuroscience"},{"issue":"3","key":"pgen.1009484.ref029","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.cell.2011.10.009","article-title":"Molecular Mechanisms of Fear Learning and Memory","volume":"147","author":"JP Joshua","year":"2011","journal-title":"Cell"},{"issue":"5","key":"pgen.1009484.ref030","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/S0092-8674(00)81904-2","article-title":"Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory","volume":"88","author":"T Abel","year":"1997","journal-title":"Cell"},{"issue":"21","key":"pgen.1009484.ref031","doi-asserted-by":"crossref","first-page":"8177","DOI":"10.1523\/JNEUROSCI.20-21-08177.2000","article-title":"Activation of ERK\/MAP Kinase in the Amygdala Is Required for Memory Consolidation of Pavlovian Fear Conditioning","volume":"20","author":"GE Schafe","year":"2000","journal-title":"The Journal of Neuroscience"},{"issue":"6","key":"pgen.1009484.ref032","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1101\/lm.1329209","article-title":"Impairments in fear conditioning in mice lacking the nNOS gene","volume":"16","author":"JB Kelley","year":"2009","journal-title":"Learning & memory (Cold Spring Harbor, NY)."},{"key":"pgen.1009484.ref033","volume-title":"Methods of Behavior Analysis in Neuroscience.","author":"P Curzon","year":"2009"},{"issue":"2","key":"pgen.1009484.ref034","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s00439-006-0197-y","article-title":"Phenotypic characterization of Bbs4 null mice reveals age-dependent penetrance and variable expressivity","volume":"120","author":"ER Eichers","year":"2006","journal-title":"Hum Genet"},{"issue":"9","key":"pgen.1009484.ref035","doi-asserted-by":"crossref","first-page":"e3000414","DOI":"10.1371\/journal.pbio.3000414","article-title":"Loss of Bardet-Biedl syndrome proteins causes synaptic aberrations in principal neurons","volume":"17","author":"N Haq","year":"2019","journal-title":"PLOS Biology"},{"issue":"10","key":"pgen.1009484.ref036","doi-asserted-by":"crossref","first-page":"e1007057","DOI":"10.1371\/journal.pgen.1007057","article-title":"BBSome function is required for both the morphogenesis and maintenance of the photoreceptor outer segment","volume":"13","author":"Y Hsu","year":"2017","journal-title":"PLoS genetics"},{"issue":"4","key":"pgen.1009484.ref037","doi-asserted-by":"crossref","first-page":"e12620","DOI":"10.1111\/gbb.12620","article-title":"The effects of tamoxifen on mouse behavior","volume":"19","author":"X Li","year":"2020","journal-title":"Genes Brain Behav"},{"issue":"15","key":"pgen.1009484.ref038","doi-asserted-by":"crossref","first-page":"6309","DOI":"10.1523\/JNEUROSCI.22-15-06309.2002","article-title":"Cortical Excitatory Neurons and Glia, But Not GABAergic Neurons, Are Produced in the Emx1-Expressing Lineage","volume":"22","author":"JA Gorski","year":"2002","journal-title":"The Journal of Neuroscience"},{"issue":"7","key":"pgen.1009484.ref039","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1093\/brain\/awl082","article-title":"Plasticity in the human central nervous system","volume":"129","author":"SF Cooke","year":"2006","journal-title":"Brain: a journal of neurology"},{"issue":"1","key":"pgen.1009484.ref040","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/0092-8674(94)90400-6","article-title":"Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein","volume":"79","author":"R Bourtchuladze","year":"1994","journal-title":"Cell"},{"issue":"14","key":"pgen.1009484.ref041","doi-asserted-by":"crossref","first-page":"8116","DOI":"10.1073\/pnas.140204597","article-title":"Deficient long-term memory and long-lasting long-term potentiation in mice with a targeted deletion of neurotrophin-4 gene","volume":"97","author":"C-W Xie","year":"2000","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"1","key":"pgen.1009484.ref042","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ajmg.a.33773","article-title":"Neocortical and hippocampal volume loss in a human ciliopathy: A quantitative MRI study in Bardet-Biedl syndrome","volume":"155a","author":"K Baker","year":"2011","journal-title":"American journal of medical genetics Part A"},{"issue":"35","key":"pgen.1009484.ref043","doi-asserted-by":"crossref","first-page":"13127","DOI":"10.1073\/pnas.0804558105","article-title":"Primary cilia regulate hippocampal neurogenesis by mediating sonic hedgehog signaling","volume":"105","author":"JJ Breunig","year":"2008","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"27","key":"pgen.1009484.ref044","doi-asserted-by":"crossref","first-page":"9933","DOI":"10.1523\/JNEUROSCI.1062-11.2011","article-title":"Primary Cilia Regulate Proliferation of Amplifying Progenitors in Adult Hippocampus: Implications for Learning and Memory","volume":"31","author":"A Amador-Arjona","year":"2011","journal-title":"The Journal of Neuroscience"},{"issue":"1","key":"pgen.1009484.ref045","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/cne.10874","article-title":"Transient expression of doublecortin during adult neurogenesis","volume":"467","author":"JP Brown","year":"2003","journal-title":"The Journal of comparative neurology"},{"issue":"12","key":"pgen.1009484.ref046","first-page":"e14382","article-title":"Lithium Improves Hippocampal Neurogenesis","volume":"5","author":"A Fiorentini","year":"2010","journal-title":"Neuropathology and Cognitive Functions in APP Mutant Mice. PLOS ONE"},{"key":"pgen.1009484.ref047","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1038\/nm.2996","article-title":"Abnormal development of NG2+PDGFR-\u03b1+ neural progenitor cells leads to neonatal hydrocephalus in a ciliopathy mouse model","volume":"18","author":"CS Carter","year":"2012","journal-title":"Nature Medicine"},{"issue":"1","key":"pgen.1009484.ref048","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1111\/j.1750-3639.2008.00246.x","article-title":"Lithium Restores Neurogenesis in the Subventricular Zone of the Ts65Dn Mouse, a Model for Down Syndrome","volume":"20","author":"P Bianchi","year":"2010","journal-title":"Brain Pathology"},{"issue":"9","key":"pgen.1009484.ref049","doi-asserted-by":"crossref","first-page":"e106576","DOI":"10.1371\/journal.pone.0106576","article-title":"Hippocampal and cortical primary cilia are required for aversive memory in mice","volume":"9","author":"NF Berbari","year":"2014","journal-title":"PLoS One"},{"issue":"4","key":"pgen.1009484.ref050","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.ymthe.2017.02.006","article-title":"Gene Therapeutic Reversal of Peripheral Olfactory Impairment in Bardet-Biedl Syndrome","volume":"25","author":"CL Williams","year":"2017","journal-title":"Molecular therapy: the journal of the American Society of Gene Therapy"},{"issue":"1","key":"pgen.1009484.ref051","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s13041-019-0466-z","article-title":"Absence of BBSome function leads to astrocyte reactivity in the brain","volume":"12","author":"M Singh","year":"2019","journal-title":"Molecular brain"},{"issue":"11","key":"pgen.1009484.ref052","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1111\/j.1460-9568.2005.04141.x","article-title":"Loss of forebrain cholinergic neurons and impairment in spatial learning and memory in LHX7-deficient mice","volume":"21","author":"A Fragkouli","year":"2005","journal-title":"The European journal of neuroscience"},{"issue":"46","key":"pgen.1009484.ref053","doi-asserted-by":"crossref","first-page":"17501","DOI":"10.1073\/pnas.0607207103","article-title":"Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus","volume":"103","author":"MD Saxe","year":"2006","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"5","key":"pgen.1009484.ref054","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1002\/hipo.20964","article-title":"4- to 6-week-old adult-born hippocampal neurons influence novelty-evoked exploration and contextual fear conditioning","volume":"22","author":"CA Denny","year":"2012","journal-title":"Hippocampus"},{"issue":"10","key":"pgen.1009484.ref055","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1038\/nn.2185","article-title":"Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain","volume":"11","author":"I Imayoshi","year":"2008","journal-title":"Nature neuroscience"},{"issue":"43","key":"pgen.1009484.ref056","first-page":"13532","article-title":"Adult-born hippocampal dentate granule cells undergoing maturation modulate learning and memory in the brain. The Journal of neuroscience: the official journal of the","volume":"29","author":"W Deng","year":"2009","journal-title":"Society for Neuroscience"},{"issue":"3","key":"pgen.1009484.ref057","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1002\/hipo.20163","article-title":"Inhibition of neurogenesis interferes with hippocampus-dependent memory function","volume":"16","author":"G Winocur","year":"2006","journal-title":"Hippocampus"},{"key":"pgen.1009484.ref058","article-title":"BBSome trains remove activated GPCRs from cilia by enabling passage through the transition zone","author":"F Ye","year":"2018","journal-title":"The Journal of Cell Biology"},{"issue":"3","key":"pgen.1009484.ref059","doi-asserted-by":"crossref","first-page":"e0195005","DOI":"10.1371\/journal.pone.0195005","article-title":"BBS1 is involved in retrograde trafficking of ciliary GPCRs in the context of the BBSome complex","volume":"13","author":"S Nozaki","year":"2018","journal-title":"PLoS ONE"},{"issue":"5","key":"pgen.1009484.ref060","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/cne.21510","article-title":"Type III adenylyl cyclase localizes to primary cilia throughout the adult mouse brain","volume":"505","author":"GA Bishop","year":"2007","journal-title":"The Journal of comparative neurology"},{"issue":"1","key":"pgen.1009484.ref061","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nn983","article-title":"Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo","volume":"6","author":"K Lai","year":"2003","journal-title":"Nature neuroscience"},{"issue":"3","key":"pgen.1009484.ref062","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/nn2059","article-title":"Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells","volume":"11","author":"YG Han","year":"2008","journal-title":"Nature neuroscience"},{"issue":"3","key":"pgen.1009484.ref063","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.neuron.2008.06.023","article-title":"TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment","volume":"59","author":"Y Li","year":"2008","journal-title":"Neuron"},{"issue":"1","key":"pgen.1009484.ref064","doi-asserted-by":"crossref","first-page":"42","DOI":"10.2174\/156720209787466028","article-title":"Brain-derived neurotrophic factor (BDNF) has proliferative effects on neural stem cells through the truncated TRK-B receptor, MAP kinase, AKT, and STAT-3 signaling pathways","volume":"6","author":"O Islam","year":"2009","journal-title":"Current neurovascular research"},{"issue":"7","key":"pgen.1009484.ref065","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1111\/gbb.12071","article-title":"Lithium treatment alleviates impaired cognition in a mouse model of fragile X syndrome","volume":"12","author":"MK King","year":"2013","journal-title":"Genes, Brain and Behavior"},{"issue":"4","key":"pgen.1009484.ref066","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1046\/j.1471-4159.2000.0751729.x","article-title":"Enhancement of hippocampal neurogenesis by lithium","volume":"75","author":"G Chen","year":"2000","journal-title":"Journal of neurochemistry"},{"issue":"4","key":"pgen.1009484.ref067","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1046\/j.1471-4159.2000.0751729.x","article-title":"Enhancement of Hippocampal Neurogenesis by Lithium","volume":"75","author":"G Chen","year":"2000","journal-title":"Journal of neurochemistry"},{"issue":"10","key":"pgen.1009484.ref068","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1001\/jamapsychiatry.2017.2362","article-title":"Association of Lithium in Drinking Water With the Incidence of Dementia","volume":"74","author":"LV Kessing","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"pgen.1009484.ref069","doi-asserted-by":"crossref","first-page":"425","DOI":"10.3389\/fnmol.2018.00425","article-title":"Lithium Treatment Is Safe in Children With Intellectual Disability.","volume":"11","author":"J Yuan","year":"2018","journal-title":"Frontiers in molecular neuroscience"},{"issue":"6","key":"pgen.1009484.ref070","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1017\/S1461145712001423","article-title":"Four weeks lithium treatment alters neuronal dendrites in the rat hippocampus","volume":"16","author":"SS Shim","year":"2013","journal-title":"International Journal of Neuropsychopharmacology"},{"issue":"1","key":"pgen.1009484.ref071","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.bbr.2012.01.016","article-title":"Lithium and valproate prevent olfactory discrimination and short-term memory impairments in the intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) rat model of Parkinson\u2019s disease.","volume":"229","author":"AA Castro","year":"2012","journal-title":"Behavioural brain research"},{"issue":"7","key":"pgen.1009484.ref072","doi-asserted-by":"crossref","first-page":"812","DOI":"10.2174\/1871527315666160801143108","article-title":"Lithium Restores Age-related Olfactory Impairment in the Ts65Dn Mouse Model of Down Syndrome","volume":"16","author":"S Guidi","year":"2017","journal-title":"CNS & neurological disorders drug targets."},{"issue":"4","key":"pgen.1009484.ref073","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.bbrc.2009.08.099","article-title":"Lithium treatment elongates primary cilia in the mouse brain and in cultured cells","volume":"388","author":"K Miyoshi","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"issue":"11","key":"pgen.1009484.ref074","doi-asserted-by":"crossref","first-page":"4242","DOI":"10.1073\/pnas.0711027105","article-title":"Bardet\u2013Biedl syndrome proteins are required for the localization of G protein-coupled receptors to primary cilia","volume":"105","author":"NF Berbari","year":"2008","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"4","key":"pgen.1009484.ref075","doi-asserted-by":"crossref","first-page":"285","DOI":"10.2174\/138920211795860134","article-title":"Keeping the balance between proliferation and differentiation: the primary cilium.","volume":"12","author":"F Irigo\u00edn","year":"2011","journal-title":"Current genomics"},{"key":"pgen.1009484.ref076","doi-asserted-by":"crossref","first-page":"e51166","DOI":"10.7554\/eLife.51166","article-title":"TTBK2 and primary cilia are essential for the connectivity and survival of cerebellar Purkinje neurons","volume":"9","author":"E Bowie","year":"2020","journal-title":"eLife"},{"issue":"11","key":"pgen.1009484.ref077","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1242\/jcs.111740","article-title":"BBS7 is required for BBSome formation and its absence in mice results in Bardet-Biedl syndrome phenotypes and selective abnormalities in membrane protein trafficking","volume":"126","author":"Q Zhang","year":"2013","journal-title":"Journal of cell science"},{"issue":"2","key":"pgen.1009484.ref078","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0014-2999(99)00573-7","article-title":"Spatial learning deficit in dopamine D(1) receptor knockout mice","volume":"383","author":"M El-Ghundi","year":"1999","journal-title":"European journal of pharmacology"},{"issue":"22","key":"pgen.1009484.ref079","doi-asserted-by":"crossref","first-page":"8245","DOI":"10.1073\/pnas.1407395111","article-title":"Differential roles of the dopamine 1-class receptors, D1R and D5R, in hippocampal dependent memory","volume":"111","author":"J Sarinana","year":"2014","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"12","key":"pgen.1009484.ref080","first-page":"4306","article-title":"Somatostatin signaling in neuronal cilia is critical for object recognition memory. The Journal of neuroscience: the official journal of the","volume":"30","author":"EB Einstein","year":"2010","journal-title":"Society for Neuroscience"},{"issue":"10","key":"pgen.1009484.ref081","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1111\/j.1460-9568.2005.04100.x","article-title":"Disrupting the melanin-concentrating hormone receptor 1 in mice leads to cognitive deficits and alterations of NMDA receptor function","volume":"21","author":"A Adamantidis","year":"2005","journal-title":"The European journal of neuroscience"},{"issue":"6","key":"pgen.1009484.ref082","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1523\/JNEUROSCI.2906-12.2013","article-title":"Arborization of Dendrites by Developing Neocortical Neurons Is Dependent on Primary Cilia and Type 3 Adenylyl Cyclase","volume":"33","author":"SM Guadiana","year":"2013","journal-title":"The Journal of Neuroscience"},{"issue":"3","key":"pgen.1009484.ref083","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.devcel.2017.07.010","article-title":"Primary Cilia Signaling Shapes the Development of Interneuronal Connectivity","volume":"42","author":"J Guo","year":"2017","journal-title":"Developmental Cell"},{"issue":"5","key":"pgen.1009484.ref084","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nm.2336","article-title":"Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning","volume":"17","author":"W Guo","year":"2011","journal-title":"Nature Medicine"},{"issue":"5","key":"pgen.1009484.ref085","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1542\/peds.2010-3500","article-title":"Health Supervision for Children With Fragile X Syndrome","volume":"127","author":"JH Hersh","year":"2011","journal-title":"Pediatrics"},{"issue":"2","key":"pgen.1009484.ref086","first-page":"454","volume":"15","author":"B Lee","journal-title":"Primary Ciliary Deficits in the Dentate Gyrus of Fragile X Syndrome. Stem Cell Reports. 2020"},{"issue":"6","key":"pgen.1009484.ref087","first-page":"550","article-title":"Circling mouse: possible animal model for deafness","volume":"51","author":"JW Lee","year":"2001","journal-title":"Comparative medicine"},{"issue":"12","key":"pgen.1009484.ref088","doi-asserted-by":"crossref","first-page":"E109","DOI":"10.1002\/lary.24174","article-title":"Mouse cochleostomy: a minimally invasive dorsal approach for modeling cochlear implantation","volume":"123","author":"H Soken","year":"2013","journal-title":"The Laryngoscope"},{"issue":"5\u20136","key":"pgen.1009484.ref089","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1159\/000241657","article-title":"Effect of lithium on reproduction and postnatal growth of mice","volume":"43","author":"DL Mroczka","year":"1983","journal-title":"Biology of the neonate"},{"issue":"6","key":"pgen.1009484.ref090","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1016\/j.celrep.2014.08.030","article-title":"P7C3 neuroprotective chemicals block axonal degeneration and preserve function after traumatic brain injury","volume":"8","author":"TC Yin","year":"2014","journal-title":"Cell reports"},{"issue":"4","key":"pgen.1009484.ref091","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1093\/beheco\/ark016","article-title":"The unequal variance t-test is an underused alternative to Student\u2019s t-test and the Mann\u2013Whitney U test","volume":"17","author":"GD Ruxton","year":"2006","journal-title":"Behavioral Ecology"},{"issue":"1","key":"pgen.1009484.ref092","doi-asserted-by":"crossref","first-page":"92","DOI":"10.5334\/irsp.82","article-title":"Why Psychologists Should by Default Use Welch\u2019s t-test Instead of Student\u2019s t-test","volume":"30","author":"M Delacre","year":"2017","journal-title":"International Review of Social Psychology"},{"issue":"Pt 1","key":"pgen.1009484.ref093","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1348\/000711004849222","article-title":"A note on preliminary tests of equality of variances","volume":"57","author":"DW Zimmerman","year":"2004","journal-title":"The British journal of mathematical and statistical psychology"}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1009484","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T11:27:09Z","timestamp":1698924429000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1009484"}},"subtitle":[],"editor":[{"given":"Gregory S.","family":"Barsh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,4,22]]},"references-count":93,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1009484","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.10.06.322883","asserted-by":"object"}]},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,22]]}}}