grant
Significance of Protein Synthesis by the Integrated Stress Response in Neuromodulatory Neurons for Adaptive Behavior and Synaptic Plasticity
NIHUS FederalResearch GrantFY2025ASDAcetylcholineAdaptive BehaviorsAffectAgingAmentiaAutismAutistic DisorderBasal GangliaBasal NucleiBehaviorBehavioralBiochemical PathwayBiologicalBrainBrain Nervous SystemBrain TraumaCaM KIICaM PK IICaM kinase IICaMKIICell BodyCell Communication and SignalingCell SignalingCellsCellular StressCellular Stress ResponseChemosensitizationChemosensitization/PotentiationCodeCoding SystemCognitiveColorConnector NeuronCorpus StriatumCorpus striatum structureD(2) Dopamine Receptor GeneD2DRD2DR GeneD2RD2R GeneDRD2DRD2 geneDataDedicationsDementiaDiseaseDisorderDopamineDopamine Receptor D2 GeneDystoniaEIF-2 alphaEIF-2alphaEIF-2αEarly Infantile AutismEncephalonEndowmentEukaryotic Initiation FactorsEukaryotic Peptide Initiation FactorsEukaryotic Translation Initiation FactorsFoundationsG Protein-Coupled Receptor SignalingGPCR SignalingGenesGeneticGenetic TechnicsGenetic TechniquesGilles de la Tourette syndromeGilles de la Tourette's DiseaseGuinon's diseaseHealthHumanHydroxytyramineInfantile AutismInitiation FactorsIntellectual disabilityIntellectual functioning disabilityIntellectual limitationIntercalary NeuronIntercalated NeuronsInterneuronsInternuncial CellInternuncial NeuronIntracellular Communication and SignalingKanner's SyndromeKinasesKnowledgeLaboratoriesLearningMediatingMemoryMemory DeficitMemory impairmentMetabolic NetworksMethodologyModalityModelingModern ManMolecularMolecular GeneticsMolecular TargetMuscle DystoniaNamesNerve CellsNerve UnitNeural CellNeurocyteNeuromodulatorNeuronsObsessive-Compulsive DisorderObsessive-Compulsive NeurosisOutcomeParalysis AgitansParkinsonParkinson DiseasePathway interactionsPeptide Initiation FactorsPhosphatasesPhosphohydrolasesPhosphomonoesterasesPhosphoric Monoester HydrolasesPhosphorylationPhosphotransferase GenePhosphotransferasesPhysiologicPhysiologicalPhysiologyPotentiationPrimary ParkinsonismProcessProtein BiosynthesisProtein PhosphorylationProteinsProteomicsRegulationReporterReportingResolutionRibosomal Peptide BiosynthesisRibosomal Protein BiosynthesisRibosomal Protein SynthesisRoleSeriesSignal TransductionSignal Transduction SystemsSignalingSiteStriate BodyStriatumSynapsesSynapticSynaptic plasticityTestingTic Disorder, Combined Vocal and Multiple MotorTourette SyndromeTourette'sTourette's DiseaseTourette's DisorderTourette's SyndromeTranscriptTranslation Initiation FactorTranslational Initiation FactorTranslationsTransphosphorylasesTraumatic Brain InjuryValidationViralVisitWorkadaptation behavioradaptive behavioraddictionaddictive disorderalpha Subunit Eukaryotic Initiation Factor 2autism spectral disorderautism spectrum disorderautistic spectrum disorderbehavioral plasticitybiologicbiological adaptation to stressbiological signal transductioncalcium-dependent CaM kinase IIcalmodulin-dependent protein kinase IIcell stresscholinergiccholinergic neurondevelop therapyexperienceexperimentexperimental researchexperimental studyexperimentsgenetic approachgenetic strategyinsightintellectual and developmental disabilityintervention developmentlearned behaviorlearning behaviorlimited intellectual functioningmaladie des ticsmemory dysfunctionnamenamednamingneural controlneural regulationneuromodulationneuromodulatoryneuronalneuroregulationpathwaypermissivenessprotein homeostasisprotein synthesisproteostasisreaction; crisisreal time monitoringrealtime monitoringresolutionsresponsesmall moleculesocial rolespatial and temporalspatial temporalspatiotemporalstress responsestress; reactionstressorstriatalsynapsesynaptic depressiontargeted drug therapytargeted drug treatmentstargeted therapeutictargeted therapeutic agentstargeted therapytargeted treatmenttherapy developmenttic de Guinontranslationtraumatic brain damagetreatment developmentvalidations
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ABSTRACT
Plasticity mechanisms endow the brain with immense capacity to adapt to a wide range of experience and
exposures. Protein synthesis, including locally at synapses, is a requirement for many forms of synaptic
plasticity. The Integrated Stress Response, ISR, is a highly conserved biochemical pathway that regulates
protein synthesis. The ISR…
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