Restoration and Further Assessment of the Actor-Critic Circuit and Connected Areas After Cocaine Self-Administration
可卡因自我给药后演员-评论家回路和连接区域的恢复和进一步评估
基本信息
- 批准号:10634903
- 负责人:
- 金额:$ 38.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-07-01 至 2028-02-29
- 项目状态:未结题
- 来源:
- 关键词:AffectAmygdaloid structureAnimalsAnteriorAreaAttentionAttenuatedBehaviorBehavioralBrainBrain regionCell CountChoice BehaviorChronicCocaineCognitiveConflict (Psychology)Corpus striatum structureCuesDataDecision MakingDevelopmentDiffusionDorsalDrug usageEnzymesEpigenetic ProcessEventExhibitsExpectancyFundingGoalsHDAC5 geneHabitsImpairmentInsula of ReilKnowledgeLateralLeadLearningMental disordersMidbrain structureModelingNational Institute of Drug AbuseNeuronsNucleus AccumbensOdorsOutcomePharmaceutical PreparationsPlayPoliciesPopulationPredictive ValueProcessPublic HealthPublishingRattusReaction TimeRelapseResearchResponse to stimulus physiologyRewardsSamplingSelf AdministrationShapesSignal TransductionStimulusStructureSystemTask PerformancesTestingTimeUncertaintyUpdateVentral Tegmental AreaWorkaddictioncareercingulate cortexcocaine exposurecocaine self-administrationcocaine usediagnostic strategydopaminergic neuroneffective therapyexecutive functionexperimental studyimprovedinnovationinsightneuralneural correlateneural repairneuromechanismneurotransmissionoptogeneticsoverexpressionpsychologicresponserestorationreward anticipation
项目摘要
PROJECT SUMMARY
Reward-guided decision-making and impulse control are disrupted after chronic cocaine use. These changes
have been attributed to altered functions in brain circuits critical for computation of reward predictions, action
policies, prediction errors and attention. ‘Reward prediction’ signals reflect the reward the animal expects to
receive as a result of behavior or presentation of a stimulus. ‘Action policies’ are rules that govern behavior that
are triggered by external stimuli or context, and are thought to underlie habits. Both reward predictions and action
policies are modified when there are violations in predictions known as ‘reward prediction errors’. ‘Signed’ reward
prediction errors reflect the valence associated with an error, strengthening or weakening the associability
between cues, responses and outcomes. ‘Unsigned’ prediction errors reflect the surprise induced by errors which
lead to increases in ‘attention’ so that learning can occur. We have uncovered neural correlates of these
constructs and the relationship between them by recording from multiple brain areas as rats perform a reward-
guided decision-making task in which we unexpectedly varied the delay to and size of reward across several
trial blocks. We have shown that nucleus accumbens core (NAc) and anterior insula (AI) encode reward
predictions, firing strongly for cues that predict more valued reward, whereas firing in dorsal lateral striatum (DLS)
is highly associative, encoding action policies such as stimulus-response associations and contextual bias
signals. We have also shown that midbrain dopamine (DA) neurons increase firing to unexpected reward and
decrease firing to unexpected reward omission. During learning these signed prediction errors transfer to cues,
with cues predicting more valued reward eliciting stronger firing. Unlike firing of DA neurons in ventral tegmental
area (VTA), our work has shown that firing in basolateral amygdala (ABL) and anterior cingulate cortex (ACC)
better reflects integrated unsigned prediction error signals and attention, increasing during unexpected up- and
down-shifts in value at the time of the error and during cue sampling on subsequent trials.
Here, we propose that activation of ACC increases attention and engages model-based mechanisms that
govern goal-directed behavior and associated mechanisms in AI, NAc and VTA, and that chronic cocaine
reduces the fidelity of reward prediction and prediction error signals, in part, by disrupting ACC function. Further,
we propose that epigenetic changes in ACC, NAc and DLS after chronic drug use alter cue selectivity in a way
that promotes fast, automatic behavior by altering the start point and rate of signals that drive actions. In this
resubmission of my renewal application we propose to further model the normal circuit and behavior, and its
disruption after cocaine-exposure by bi-directionally manipulating neural signals via optogenetics and epigenetic
(histone deacetylase 5, HDAC5) manipulation. By performing these experiments, we will gain further insight into
how the brain functions normally, how it is disrupted after chronic cocaine use, and determine if repairing neural
signals in ACC and striatum might restore behavior and neural constructs in downstream regions.
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)
会议论文数量(0)
专利数量(0)
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MATTHEW R ROESCH其他文献
MATTHEW R ROESCH的其他文献
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{{ truncateString('MATTHEW R ROESCH', 18)}}的其他基金
CRCNS:US-Fr Research: Neurobehavioral Assessment of a Reward Learning Model
CRCNS:US-Fr 研究:奖励学习模型的神经行为评估
- 批准号:
9052451 - 财政年份:2015
- 资助金额:
$ 38.08万 - 项目类别:
CRCNS:US-Fr Research: Neurobehavioral Assessment of a Reward Learning Model
CRCNS:US-Fr 研究:奖励学习模型的神经行为评估
- 批准号:
9143067 - 财政年份:2015
- 资助金额:
$ 38.08万 - 项目类别:
Neural mechanisms underlying social recognition of reward
奖励社会认可的神经机制
- 批准号:
8990990 - 财政年份:2015
- 资助金额:
$ 38.08万 - 项目类别:
Neural mechanisms underlying social recognition of reward
奖励社会认可的神经机制
- 批准号:
8821334 - 财政年份:2015
- 资助金额:
$ 38.08万 - 项目类别:
CRCNS:US-Fr Research: Neurobehavioral Assessment of a Reward Learning Model
CRCNS:US-Fr 研究:奖励学习模型的神经行为评估
- 批准号:
9313241 - 财政年份:2015
- 资助金额:
$ 38.08万 - 项目类别:
Impact of cocaine on the Actor/Critic circuit
可卡因对演员/评论家电路的影响
- 批准号:
8654324 - 财政年份:2011
- 资助金额:
$ 38.08万 - 项目类别:
Restoration and Further Assessment of the Actor-Critic Circuit and Connected Areas After Cocaine Self-Administration
可卡因自我给药后演员-评论家回路和连接区域的恢复和进一步评估
- 批准号:
9412155 - 财政年份:2011
- 资助金额:
$ 38.08万 - 项目类别:
Impact of cocaine on the Actor/Critic circuit
可卡因对演员/评论家电路的影响
- 批准号:
8280446 - 财政年份:2011
- 资助金额:
$ 38.08万 - 项目类别:
Restoration and Further Assessment of the Actor-Critic Circuit and Connected Areas After Cocaine Self-Administration
可卡因自我给药后演员-评论家回路和连接区域的恢复和进一步评估
- 批准号:
10087906 - 财政年份:2011
- 资助金额:
$ 38.08万 - 项目类别:
Impact of cocaine on the Actor/Critic circuit
可卡因对演员/评论家电路的影响
- 批准号:
8459880 - 财政年份:2011
- 资助金额:
$ 38.08万 - 项目类别: