Molecular Mechanisms Influencing Aggressive Behaviours: Novartis Foundation Symposium 268 PDF
Preview Molecular Mechanisms Influencing Aggressive Behaviours: Novartis Foundation Symposium 268
Molecular Mechanisms Influencing Aggressive Behaviours: Novartis Foundation Symposium 268, Volume 268. Edited by Gregory Bock and Jamie Goode Copyright Novartis Foundation 2005. ISBN: 0-470-01068-1 MOLECULAR MECHANISMS INFLUENCING AGGRESSIVE BEHAVIOURS TheNovartisFoundationisaninternationalscienti¢candeducational charity(UKRegisteredCharityNo.313574).KnownuntilSeptember1997 astheCibaFoundation,itwasestablishedin1947bytheCIBAcompany ofBasle,whichmergedwithSandozin1996,toformNovartis.The FoundationoperatesindependentlyinLondonunderEnglishtrust law.Itwasformallyopenedon22June1949. TheFoundationpromotesthestudyandgeneralknowledgeof scienceandinparticularencouragesinternationalco-operationin scienti¢cresearch.Tothisend,itorganizesinternationally acclaimedmeetings(typicallyeightsymposiaandalliedopen meetingsand15^20discussionmeetingseachyear)andpublishes eightbooksperyearfeaturingthepresentedpapersanddiscussions fromthesymposia.Althoughprimarilyanoperationalratherthan agrant-makingfoundation,itawardsbursariestoyoungscientists toattendthesymposiaandafterwardsworkwithoneoftheother participants. TheFoundation’sheadquartersat41PortlandPlace,LondonW1B1BN, providelibraryfacilities,opentograduatesinscienceandallieddisciplines. Mediarelationsarefosteredbyregularpressconferencesandbyarticles preparedbytheFoundation’sScienceWriterinResidence.TheFoundation o¡ersaccommodationandmeetingfacilitiestovisitingscientistsandtheir societies. 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Contents SymposiumonMolecularmechanismsin£uencingaggressivebehaviours,heldattheNovartis Foundation,London,20^22July2004 Editors:GregoryBock(Organizer)andJamieGoode ThismeetingwasbasedonaproposalmadebyDonaldPfa¡,BarryKeverneandRandyNelson DonaldPfa¡ Introduction 1 RobertJ.BlanchardandD.CarolineBlanchard Somesuggestionsforrevitalizing aggressionresearch 4 Discussion 13 RobinLovell-Badge Aggressivebehaviour:contributionsfromgenesonthe Ychromosome 20 Discussion 33 DianeM.Robins Androgenreceptorandmolecularmechanismsofmale-speci¢c geneexpression 42 Discussion 53 EdwardS.Brodkin Quantitativetraitlocusanalysisofaggressivebehavioursin mice 57 Discussion 69 DonaldPfa¡,ElenaCholerisandSonokoOgawa Genesforsexhormone receptorscontrollingmouseaggression 78 Discussion 89 GeneraldiscussionI 96 CatherineDulac Moleculararchitectureofpheromonesensinginmammals 100 Discussion 107 Klaus-PeterLesch Serotonergicgeneinactivationinmice:modelsforanxietyand aggression? 111 Discussion 140 v vi CONTENTS RandyJ.Nelson E¡ectsofnitricoxideontheHPAaxisandaggression 147 Discussion 160 GeneraldiscussionII 167 BerendOlivier Serotonergicmechanismsinaggression 171 Discussion 183 CraigF.Ferris Vasopressin/oxytocinandaggression 190 Discussion 198 ManuelaMartinezandConcepcio¤nBlasco-Ros Typologyofhumanaggression anditsbiologicalcontrol 201 Discussion 208 StephenJ.Suomi Aggressionandsocialbehaviourinrhesusmonkeys 216 Discussion 222 IanW.Craig TheroleofmonoamineoxidaseA(MAOA)intheaetiologyof antisocialbehaviour:theimportanceofgene^environmentinteractions 227 Discussion 237 Finaldiscussion 242 Indexofcontributors 254 Subjectindex 256 Participants D.CarolineBlanchard UniversityofHawaii,DepartmentofPsychology, CollegeofSocialSciences,Gartley110,2430CampusRoad,Honolulu, HI96822,USA RobertJ.Blanchard UniversityofHawaii,DepartmentofPsychology,College ofSocialSciences,Gartley110,2430CampusRoad,Honolulu,HI96822,USA Bj˛rnBrembs InstitutfˇrNeurobiologie,FUBerlin,K˛nigin-Luise-Str. 28/30,D-14195Berlin,Germany EdwardS.Brodkin UniversityofPennsylvaniaSchoolofMedicine,Centerfor NeurobiologyandBehavior,415CurieBoulevard,Room111,Philadelphia, PA19104-6140,USA IanCraig POBox82,SGDPResearchCentre,InstituteofPsychiatry, DeCrespignyPark,DenmarkHill,LondonSE58AF,UK CatherineDulac DepartmentofMolecularandCellularBiology, HarvardUniversity,16DivinityAvenue,Cambridge,MA02138,USA CraigFerris DepartmentofPsychiatry,UniversityofMassachusettsMedical School,55LakeAvenueNorth,Worcester,Massachusetts01655,USA StephenGammie 1117WestJohnsonSt,ZoologyResearchBuilding, Room213,DepartmentofZoology,UniversityofWisconsin,Madison, WI 53706,USA RobertHinde StJohn’sCollege,CambridgeCB21TP,UK BarryKeverne Sub-DepartmentofAnimalBehaviour,Universityof Cambridge,HighStreet,Madingley,CambridgeCB38AA,UK JaapKoolhaas DepartmentofAnimalPhysiology,UniversityofGroningen, P.O.Box14,9750AAHaren,TheNetherlands vii viii PARTICIPANTS Klaus-PeterLesch KlinikundPoliklinikfˇrPsychiatrieundPsychotherapie, Universit(cid:1)tWˇrzburg,D-97080Wˇrzburg,Germany RobinLovell-Badge TheNationalInstituteforMedicalResearch, TheRidgeway,MillHill,LondonNW71AA,UK StephenManuck BehavioralPhysiologyLaboratory,Departmentof Psychology,UniversityofPittsburgh,506OldEngineeringHall,Pittsburgh, PA15260,USA ManuelaMartinez DepartmentofPsychobiology,FacultyofPsychology, UniversityofValencia,Avda.BlascoIba•ez21,46010,Valencia,Spain RandyNelson DepartmentsofPsychologyandNeuroscience,09Townshend Hall,TheOhioStateUniversity,Columbus,OH 43210,USA BerendOlivier DepartmentofPsychopharmacology,UtrechtInstitutefor PharmaceuticalSciences,UtrechtUniversity,Sorbonnelaan16,3584CA, Utrecht,TheNetherlands DonaldPfa¡ (Chair) NeurobiologyandBehavior,TheRockefellerUniversity, Box275,1230YorkAvenue,NewYork,NY10021-6399,USA DianeM.Robins DepartmentofHumanGenetics,UniversityofMichigan, 4909Buhl,1241E.CatherineSt,AnnArbor,MI48109-0618,USA DavidSkuse BehaviouralandBrainSciencesUnit,InstituteofChildHealth, 30GuilfordStreet,LondonWC1N1EH,UK StephenSuomi NationalInstituteofChildHealthandHumanDevelopment, 31CenterDrive,Bethesda,MD20892,USA BrianTrainor(NovartisFoundationBursar) BauerCenterforGenomicsResearch, HarvardUniversity,7DivinityAvenue,Cambridge,MA02138,USA Molecular Mechanisms Influencing Aggressive Behaviours: Novartis Foundation Symposium 268, Volume 268. Edited by Gregory Bock and Jamie Goode Copyright Novartis Foundation 2005. ISBN: 0-470-01068-1 Introduction DonaldPfa¡ Neurobiology and Behavior, The Rockefeller University, Box 275, 1230 York Avenue, NewYork,NY10021-6399,USA In this introduction I’d like to state some questions that might deserve consideration during this meeting. To try to do so in a comprehensive way would be presumptuous of me. So I have, o¡ the top of my head, listed some back of the envelope questions that might put some of our discussions in a historical context, and then I will ask Robert Hinde, Barry Keverne and Randy Nelsontoaddconsiderationsthattheymighthave. My¢rstquestionmightbetitled‘Beyondtranscription’.Certainly,withrespect toandrogenice¡ectsonaggressivebehaviours,upuntilnowithasbeeneasiestto ascribe regulatory in£uences of hormones to transcriptional changes. This was naturalforaneurobiologisttodobecausethechemistryofDNAissimplerthan thatofmostothercellularcompounds.Until1944,whenDNAwasdiscoveredto be the genetic substance, it was considered to be a stupid molecule(cid:1)much too stupidtocarrythegeneticinformation.Somyquestionis,towhatextentcanwe envisionfacingthedi⁄cultiesofdealingwithRNAeditingandproteinchemistry in neurons as part of the business of life, with respect to molecular mechanisms underlyingaggression? Second,howarewegoingtoanalysetheindirectaswellasthedirectin£uenceof genomic changes on aggressive behaviours? In 1941, working with Neurospora, Beadle and Tatum came up with data that supported the one gene/one enzyme concept. I would argue that up until a few years ago, the one gene one enzyme concept dominated functional genomics, but with respect to sex behaviours whereweknowanawfullot,Ihavebeenabletoarguethatwearealwaysdealing with patterns of gene expression governing patterns of sociosexual behaviours. Howdoweapplythiskindofthinkingtoaggression? Finally, ethology is the science of behaviour. I for one aspire to the kind of precisionandlawfulnessthatwe¢ndinthephysicalsciences.Towhatextentdo the stereopathies of aggressive behaviour, and their obvious biological adaptiveness(atleastinanimals),provideoneofthebestsubjectsforustoprove thatbehaviouralsciencecanachievethesamekindoflawfulnessandprecisionas thephysicalsciences?I’llnowaskRobertHindewhathopesorwarningshemight haveforus. 1 2 PFAFF Hinde:Iamamis¢tatthismeetingbecauseIhaven’tworkedbelowtheskinfor 40years,letaloneatthemolecularlevel.ButIamoftheopinionthatviolenceis perhapsthemostimportantproblemhumansface.WhatIwillbelookingforisthe following.Arewemakingacleardistinctionbetweenaggression(whichisusually in human studies de¢ned as the intentional a¥iction of harm on another individual), and aggressiveness (the propensity to be aggressive). One is an act, the other is a general propensity. Second, are we making a clear distinction betweenthevarioustypesofaggression?Theseincludeinstrumentalorfelonious aggression, teasing aggression, revenge aggression and socially acceptable aggression that is condoned in a gang or small group but not in the general population, and so on. This approximates to what Donald Pfa¡ calls the ‘form’ of aggression, when he makes the distinction between testosterone-instigated and maternal aggression. During the papers I shall be thinking of whether it is the motor pattern that is being studied (and some of the subjects are chosen because of the stereotyped nature of mouse aggression which makes it easy to score)orisitthepropensitytouseviolencewithanysortofmotivation,orisit motivationbeingstudiedinaparticularcontext. Keverne:Wehaveabroadaudiencehereofresearchersstudyingsubjectsranging from£iestohumans.Thereisnodoubtthatmanyofthesamegenescrossallof thesebiologicalgroups.Itisimportanttobearinmindthatwiththecloningand sequencing of the human and mouse genome, we now know that both have approximately the same number of genes. Actually, humans have slightly fewer than the mouse, and the ones we lack are primarily in the olfactory system. We also know that there is 96% sequence synteny. Clearly, these similar genes and sequences are building very di¡erent phenotypes. It is important for us to take intoaccounthowdi¡erentthesephenotypesare,particularlywithrespecttothe brain and brain development. One of the things that is di¡erent between the human brain and the small rodent brain is that our behaviour is not primarily directed by olfactory cues. Secondly, most of the development in our brains occursinthepostnatalenvironment,anditoccursatatimewhenwearelearning thesocialcuesofhowtocontrolandregulateourbehaviour.Evolutionarily,this developmentofthebrainisnotinsigni¢cantwhenwetrytotransferinformation fromwhatisknowninthe£yormousetothehuman.Atthetranscriptionallevelof agivengeneitisgoingtoberemarkablysimilar,butintermsofwhatthegenomeis doing in building a phenotype, it is going to be di¡erent, and in terms of what humanscandowiththatphenotypeisalsoverydi¡erent.Forexample,muchof human behaviour is to some extent emancipated from hormonal in£uences. Women do not need to have undertaken pregnancy and parturition to be good mothers. We don’t wait until we get the hunger signals from hormones before wefeed.Wedoourforaginginasupermarketinadvanceofhunger.Aggression isevenmorecomplexbecauseitinvariablyneedsacontext.Itisrarelyspontaneous
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