Targeting computation in prefrontal cortex to improve decision-making and reduce compulsive drinking in rodent models.
针对前额皮质的计算,以改善啮齿动物模型中的决策并减少强迫性饮酒。
基本信息
- 批准号:10675561
- 负责人:
- 金额:$ 43.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-10 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectAlcohol abuseAlcohol consumptionAlcohol dependenceAlcoholsAnimal ModelAnimalsBehaviorBehavior ControlBehavioralBiologicalBrainBrain regionChronicComputational TechniqueComputer ModelsCuesDataDecision MakingDevelopmentDiagnosisElectrophysiology (science)ExhibitsFamilyFamily history ofFunctional disorderFutureGeneticGoalsHeavy DrinkingHeterogeneityHumanImpairmentImpulsive BehaviorImpulsivityIndividualMeasuresMeta-AnalysisModelingMyopiaNeuronsNeurophysiology - biologic functionPathologyPharmacotherapyPlayPredisposing FactorPrefrontal CortexPrevalenceProceduresProcessQuinineRecording of previous eventsResearchRewardsRiskRisk FactorsRodentRodent ModelRoleSeriesSex DifferencesSystemTechniquesTestingWorkaddictionalcohol consequencesalcohol exposurealcohol use disorderawakebehavior measurementbehavioral impairmentbehavioral phenotypingcell typechronic alcohol ingestioncortical catecholaminedata modelingdesigndesigner receptors exclusively activated by designer drugsdisorder riskdrinkingexperimental studyfunctional restorationgenetic approachgenetic risk factorhuman datahuman modelhuman subjectimprovedneuralneural circuitneural correlateneural patterningnovelnovel strategiespre-clinicalpreclinical studyprogramspsychologicremediation
项目摘要
Project Summary
Impairments in decision-making are both a risk factor for and consequence of an Alcohol Use Disorder (AUD).
These impairments are particularly debilitating as there are currently no approved pharmacotherapies
designed to improve this aspect of an AUD. Impulsivity is a behavioral phenotype that reflects alterations in the
decision-making process and is broadly characterized as the tendency to act without foresight and can be
fractionated into several different subtypes. Non-planning impulsivity is a subtype of impulsivity characterized
by the tendency to make decisions in a way that is not guided by plans or future goals. In addition, of all
impulsivity subtypes a recent meta-analysis indicates that non-planning impulsivity is a strong predictor of
alcohol dependence in humans. Therefore, there is a critical need to explore the neural basis of planning and
impulsivity to inspire novel treatment approaches capable of addressing this pathology. In addition, previous
work from our group in rodents converges with data from human subjects that indicates targeting the prefrontal
cortex (PFC) may provide an effective way to reduce addiction-associated behaviors. The overarching
hypothesis of this project is that targeting the pathology of the PFC will rescue impairments in
decision-making observed in rodent models of AUD. A series of preclinical studies are proposed that will
use rigorous and cutting-edge techniques to measure and manipulate neural activity in awake, behaving
rodents. Heterogeneity in the animal models used will broaden the impact of the results by making them
applicable to those with and without family history/genetic risk factors for problematic alcohol use as well as
sex differences. Our previous work and preliminary data indicate that neural and behavioral signatures of
planning are disrupted in excessive drinking animals. To explore the neural basis of this disruption and how to
fix it, designer receptors exclusively activated by designer drugs (DREADDs) will be used to target and
manipulate the activity of PFC neurons during behavior. In addition, large scale neural recordings from the
PFC will be performed while animals are engaged in behavioral tasks designed to either measure impulsivity or
the decision to consume alcohol. Finally, novel and rigorous statistical procedures and computational modeling
approaches will be used to analyze the neural recordings obtained. These approaches will create a generative
model of the data and therefore provide a detailed picture of the computations performed by these neurons. In
this way, a clear mechanistic picture of the role that PFC neurons play in guiding behavior will be created by
establishing causal inference between neural activity and behavior. In summary, the proposed work will identify
how decision-making is altered in rodent models of AUD and how to improve it. This work will bring this
program of research closer to its long-term goal of inspiring novel targets for treatment that are capable of
addressing impaired decision-making in AUD.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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专利数量(0)
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{{ truncateString('CRISTINE L CZACHOWSKI', 18)}}的其他基金
Targeting computation in prefrontal cortex to improve decision-making and reduce compulsive drinking in rodent models.
针对前额皮质的计算,以改善啮齿动物模型中的决策并减少强迫性饮酒。
- 批准号:
10277796 - 财政年份:2021
- 资助金额:
$ 43.2万 - 项目类别:
Neurobehavioral Assessment of Ethanol Seeking and Intake in the Rat
大鼠乙醇寻求和摄入的神经行为评估
- 批准号:
7900413 - 财政年份:2007
- 资助金额:
$ 43.2万 - 项目类别:
Neurobehavioral Assessment of Ethanol Seeking and Intake in the Rat
大鼠乙醇寻找和摄入的神经行为评估
- 批准号:
8112588 - 财政年份:2007
- 资助金额:
$ 43.2万 - 项目类别:
Neurobehavioral Assessment of Ethanol Seeking and Intake in the Rat
大鼠乙醇寻找和摄入的神经行为评估
- 批准号:
7322752 - 财政年份:2007
- 资助金额:
$ 43.2万 - 项目类别:
Neurobehavioral Assessment of Ethanol Seeking and Intake in the Rat
大鼠乙醇寻求和摄入的神经行为评估
- 批准号:
7661711 - 财政年份:2007
- 资助金额:
$ 43.2万 - 项目类别:
Neurobehavioral Assessment of Ethanol Seeking and Intake in the Rat
大鼠乙醇寻找和摄入的神经行为评估
- 批准号:
7503393 - 财政年份:2007
- 资助金额:
$ 43.2万 - 项目类别:
Drug Treatment of Ethanol Seeking in Rat and Monkey
大鼠和猴子乙醇寻求的药物治疗
- 批准号:
6744813 - 财政年份:2003
- 资助金额:
$ 43.2万 - 项目类别:
Drug Treatment of Ethanol Seeking in Rat and Monkey
大鼠和猴子乙醇寻求的药物治疗
- 批准号:
6890366 - 财政年份:2003
- 资助金额:
$ 43.2万 - 项目类别:
Drug Treatment of Ethanol Seeking in Rat and Monkey
大鼠和猴子乙醇寻求的药物治疗
- 批准号:
7057318 - 财政年份:2003
- 资助金额:
$ 43.2万 - 项目类别:
Drug Treatment of Ethanol Seeking in Rat and Monkey
大鼠和猴子乙醇寻求的药物治疗
- 批准号:
6555572 - 财政年份:2003
- 资助金额:
$ 43.2万 - 项目类别:
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