Abstract

Clinicaldisordersarisingfrommaladaptiveemotionregulationpresentalargeburdenonsociety worldwide.Manyofthesedisordersshowcomorbidity,forexample,addictionwithanxietydisorders. Cuespredictingsomethingaversiveelicitavoidanceandfearbehaviorswhereascuespredicting rewardelicitapproachandreward-seekingbehaviors.Cuessignifyingsafetyhavethepowerto modulatefearandreward-seekingbehaviorsbyinformingtheorganismwhetherornottheenvironment issafe.Thus,safety,fearandrewardbehaviors,andthecircuitriesgoverningthesebehaviors,are intertwined.Themajorityofstudiesonrewardandfearprocessinghavebeenconductedinparallel, investigatingthecircuitriesseparatelyinprimarilymalesubjects.Ifwehopetounderstandandtreat comorbiddisordersresultingfrommaladaptiveemotionregulationincreasedeffortsininvestigatinghow thesecircuitriesintegratetheirfunctionstoinfluencebehaviorisneededinbothmaleandfemale subjects.Theproposedworkusesanovelbehavioralparadigmexplicitlydesignedtoassesssafety, fearandrewardcuelearningtogetherinordertoinvestigatethemultiplecircuitriesthatregulatethese learningprocessesinaratmodel.Ourresultsshowthat,comparedtomales,femaleratsdonotshow suppressionofconditionedfearinthepresenceofthesafetycue,indicatingafailuretoregulatefearin ?safe?conditions,andtheyaremorerewardresponsiveduringtherewardcue.Sincewomenaremore thantwiceaslikelyasmentodevelopemotiondysregulationdisorders,thisparadigmoffersagreat opportunitytoteaseapartthesexdifferencesinneuralcircuitrythataregeneratingthebehavioralsex differences.Together,theproposedaimsaredesignedtoidentifytheneuralcircuitryandmechanisms ofsafety,fearandrewardcuediscriminationandhowtheymaydifferbetweenmalesandfemales.
Aims1 and2focusontheinfralimbicprefrontalcortex,prelimbicprefrontalcortexandbasolateral amygdalainmaleandfemaleratstoidentifydifferencesinneuralactivityandthecriticalprojections amongthesebrainregionsduringsafety-fear-rewarddiscrimination.
Aim3 focusesontheprojection fromtheventraltegmentalareatothebasolateralamygdalainmaleandfemalerats.Weexpectto advanceourunderstandingoftheneuralcircuitrymediatingdiscriminationamongemotionallyrelevant environmentalcuesinbothmaleandfemalesubjects,therebyincreasingourknowledgeata systems/circuitslevelofpossiblesexdifferencesinemotionaldisorders.Determininghowneuralcircuit sexdifferencesaregeneratingsexdifferencesinsafety-fear-rewarddiscriminationwillimprovefuture developmentofsex-specificbehavioralanddrugtreatmentsinindividualsdiagnosedwithemotion dysregulationdisorders.

Public Health Relevance

Eventhoughtherehasbeenmuchresearchonrewardandfearprocessing,themajorityofstudieshavebeen conductedinparallel,investigatingtheneuronalcircuitriesseparatelyinprimarilymalesubjects.Ifwehopeto understandandtreatcomorbiddisordersresultingfrommaladaptiveemotionregulationweneedtoincrease oureffortsininvestigatinghowthesecircuitsintegratetheirfunctionstoinfluencebehavior.Ournovel behavioralparadigmdesignedtoassessreward,fearandsafetylearningtogethershowsexdifferencesinfear andrewardbehaviors,makingitapowerfultooltoinvestigatetheneuronalcircuitryregulatingtheselearning processesinmalesversusfemales.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH110425-02
Application #
9659378
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Vicentic, Aleksandra
Project Start
2018-03-02
Project End
2022-12-31
Budget Start
2019-01-01
Budget End
2019-12-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost

  Institution

Name
Purdue University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907