A genome-wide screen identifies PAPP-AA-mediated IGFR signaling as a novel regulator of habituation learning

Neuron
Marc A WolmanMichael Granato

Abstract

Habituation represents a fundamental form of learning, yet the underlying molecular genetic mechanisms are not well defined. Here we report on a genome-wide genetic screen, coupled with whole-genome sequencing, that identified 14 zebrafish startle habituation mutants including mutants of the vertebrate-specific gene pregnancy-associated plasma protein-aa (pappaa). PAPP-AA encodes an extracellular metalloprotease known to increase IGF bioavailability, thereby enhancing IGF receptor signaling. We find that pappaa is expressed by startle circuit neurons, and expression of wild-type but not a metalloprotease-inactive version of pappaa restores habituation in pappaa mutants. Furthermore, acutely inhibiting IGF1R function in wild-type reduces habituation, while activation of IGF1R downstream effectors in pappaa mutants restores habituation, demonstrating that pappaa promotes learning by acutely and locally increasing IGF bioavailability. In sum, our results define the first functional gene set for habituation learning in a vertebrate and identify PAPPAA-regulated IGF signaling as a novel mechanism regulating habituation learning.

References

Sep 29, 1978·Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character·H KornD S Faber
Mar 1, 1992·Archives of General Psychiatry·D L BraffM A Geyer
Feb 12, 1990·Behavioural Brain Research·C H RankinC M Chiba
Jan 15, 1974·American Journal of Obstetrics and Gynecology·T M LinS Gall
Sep 1, 1970·Psychological Review·P M Groves, R F Thompson
Jan 1, 1974·Developmental Psychobiology·C B KimmelR O Kimmel
Jan 1, 1966·Psychological Review·R F Thompson, W A Spencer
Feb 1, 1968·The Journal of the Acoustical Society of America·H S Hoffman, J L Searle
Apr 4, 1983·Brain Research·J T Hackett, D S Faber
Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·M A Castro-Alamancos, I Torres-Aleman
Jan 1, 1994·The Journal of Comparative Neurology·J W ScottH Korn
Jul 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·C B KimmelT F Schilling
Feb 25, 1998·Behavioural Brain Research·M Koch, H U Schnitzler
Mar 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·J B LawrenceC A Conover
May 5, 1999·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·B AnlarE L Feldman
May 18, 1999·Molecular and Cellular Neurosciences·E J Williams, P Doherty
Feb 13, 2001·Progress in Neurobiology·R C EatonM B Foreman
Mar 20, 2003·Behavioural Brain Research·Gernot RiedelJacques Micheau
Apr 26, 2003·The European Journal of Neuroscience·Susanne SchmidHans-Ulrich Schnitzler
Jan 24, 2004·The EMBO Journal·Suparna SanyalHubert H M Van Tol
Jun 24, 2004·Cognitive and Behavioral Neurology : Official Journal of the Society for Behavioral and Cognitive Neurology·Eva M JansiewiczStewart H Mostofsky
Aug 4, 2004·Psychoneuroendocrinology·Christian BenedictWerner Kern
Sep 22, 2005·Experimental and Clinical Psychopharmacology·Frances K McSweeneyBenjamin P Kowal
Sep 1, 1967·Proceedings of the National Academy of Sciences of the United States of America·S Benzer
Jul 13, 2006·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Leif HertzGerald A Dienel
Nov 10, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jacqueline K Rose, Catharine H Rankin
Mar 10, 2007·Current Pharmaceutical Design·Luigi LaviolaFrancesco Giorgino
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Fred W WolfUlrike Heberlein
May 4, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Harold A Burgess, Michael Granato
Jul 3, 2007·The Journal of Experimental Biology·Harold A Burgess, Michael Granato
Aug 23, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Stephan BickelDaniel Umbricht
Sep 28, 2007·The American Journal of Psychiatry·Ganesan VenkatasubramanianK Taranath Shetty
Apr 3, 2008·Proceedings of the National Academy of Sciences of the United States of America·Daisuke D IkedaYuichi Iino
Jul 11, 2008·The Biochemical Journal·Sarawut JitrapakdeePaul V Attwood

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Citations

Feb 5, 2016·ACS Chemical Biology·Matthew N McCarrollDavid Kokel
Nov 10, 2015·Neuron·Jesse Isaacman-BeckMichael Granato
Mar 20, 2015·Neuron·Evan L Ardiel, Catharine H Rankin
Jul 12, 2016·Neuron·Carlos PantojaEhud Y Isacoff
Apr 10, 2017·Current Opinion in Neurobiology·Grigorios Oikonomou, David A Prober
Mar 29, 2019·Biomedicines·Ram Manohar BasnetMaurizio Memo
May 23, 2017·ELife·Adam C MillerCecilia B Moens
Jun 1, 2019·Communications Biology·Juliane BremerMichael Granato
Jan 12, 2020·Communications Biology·Juliane BremerMichael Granato
Feb 23, 2021·Frontiers in Cell and Developmental Biology·Melanie Holmgren, Lavinia Sheets
Jun 6, 2020·Current Biology : CB·Jessica C NelsonMichael Granato
Apr 9, 2021·Frontiers in Neural Circuits·Dániel BátoraAndrás Málnási-Csizmadia
Mar 21, 2021·G3 : Genes - Genomes - Genetics·Dana Klatt Shaw, Mayssa H Mokalled
Apr 29, 2021·ELife·Abagael M LasseigneAdam C Miller
Apr 29, 2021·Journal of the Association for Research in Otolaryngology : JARO·Lavinia SheetsKatie S Kindt
Jun 8, 2021·Frontiers in Neuroscience·Massimo M OnestoTimothy M Gomez
Aug 3, 2021·Frontiers in Molecular Neuroscience·Laura Corradi, Alessandro Filosa
Aug 9, 2020·Current Biology : CB·Carlos PantojaHerwig Baier

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