Neural circuit elements that orchestrate cue-reward associations
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Principal Investigator: Garret D Stuber Organization: UNIVERSITY OF WASHINGTON Fiscal Year: 2024 Award: $455,615 Funding agency: National Institute on Drug Abuse The neural circuitry that encodes and mediates the establishment of cue-reward associations, an adaptive process that is essential for survival, likely becomes dysfunctional in neuropsychiatric illnesses such as drug addiction. While the full encoding of cue-reward associations require a distributed network of brain nuclei acting in concert to orchestrate behavioral output, neurons in ventral tegmental area and upstream circuits in cortex and hypothalamus are thought to play an important role in reward prediction and assigning incentive salience to environmental cues such as those that become associated with repeated drug use. In this application, we propose to state of the art deep brain two-photon imaging in awake and behaving mice to study how the encoding properties within these circuits emerge and are altered during primary reward exposure as well in associative learning. These experiments will provide important mechanistic information to explain how reward circuits encode and control the development and expression of cue-reward associations relevant to addiction. Terms: <2-photon><2-photon microscopy><Adaptive Behaviors><Animals><Aquadiol><Association Learning><Associative Learning><Award><Behavior><Behavioral><Brain><Brain Nervous System><Brain region><CRISPR><CRISPR/Cas system><Cell Body><Cell Communication and Signaling><Cell Nucleus><Cell Signaling><Cells><Chemical Dependence><Clustered Regularly Interspaced Short Palindromic Repeats><Complex><Cues><Data><Data Set><Decision Making><Dependence><Development><Diagnosis><Dimenformon><Diogyn><Diogynets><Disease><Disorder><Drug Addiction><Drug Dependence><Drug Dependency><Drug usage><Drugs><Elements><Emotions><Encephalon><Estrace><Estradiol><Estradiol-17 beta><Estradiol-17beta><Estraldine><Female><Funding><Gene Expression><Genes><Genetic><Goals><Habenula><Hormonal><Hypothalamic structure><Hypothalamus><Image><Intracellular Communication and Signaling><Knock-out><Knockout><Lateral><Learning><Link><Mediating><Medication><Mental disorders><Mental health disorders><Methods><Mice><Mice Mammals><Molecular><Molecular Genetics><Murine><Mus><Nerve Cells><Nerve Unit><Nervous System Diseases><Nervous System Disorder><Neural Cell><Neurobiology><Neurocyte><Neurologic Disorders><Neurological Disorders><Neurons><Nucleus><Opsin><Optics><Output><Ovocyclin><Ovocylin><Pain><Painful><Pattern><Pavlovian conditioning><Pharmaceutical Preparations><Physiologic><Physiological><Play><Population><Procedures><Process><Progynon><Property><Psychiatric Disease><Psychiatric Disorder><Pyramidal neuron><Research><Rewards><Rod-Opsin><Role><Self Administered><Self Administration><Sensory><Signal Transduction><Signal Transduction Systems><Signaling><Societies><Steroid Compound><Steroids><Stimulus><Substance abuse problem><Technology><Testing><Testosterone><Therapeutic Estradiol><Therapeutic Testosterone><Time><Trans-Testosterone><Universities><Ventral Tegmental Area><Viral><Virus><Washington><Work><abuse of substances><adaptation behavior><adaptive behavior><addiction><addictive disorder><associative conditioning><awake><biological signal transduction><calcium indicator><cell assembly><cell type><classical conditioning><conditioning><design><designing><developmental><drug use><drug/agent><experiment><experimental research><experimental study><experiments><hippocampal pyramidal neuron><holographic stimulation><hormonal signals><hormone signals><hypothalamic><imaging><improved><incentive salience><instrumentation><interest><lens><lenses><maladaptive behavior><male><mental illness><molecular biomarker><molecular marker><motivated behavior><neural><neural circuit><neural circuitry><neural patterning><neurobiological><neurocircuitry><neurological disease><neuronal><neuropsychiatric><neuropsychiatric disease><neuropsychiatric disorder><neuropsychiatry><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><next generation><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><optical><optogenetics><psychiatric illness><psychological disorder><scRNA-seq><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell transcriptomic profiling><single-cell RNA sequencing><social role><substance abuse><synaptic circuit><synaptic circuitry><two photon excitation microscopy><two photon microscopy><two-photon><ventral tegmentum>