权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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：
9412155
负责人：
MATTHEW R ROESCH
金额：
$ 31.99万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
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 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9412155
关键词：
Affect Amygdaloid structure Animals Anterior Area Attention Behavior Behavior Control Brain Brain region Chronic Cocaine Corpus striatum structure Cues Decision Making Dependence Development Diagnostic Dopamine Dorsal Drug usage Equilibrium Event Goals Habits Hypersensitivity Hypersensitivity skin testing Impairment Impulsivity Investigation Knowledge Lateral Lead Learning Lesion Marshal Mental disorders Midbrain structure Modeling National Institute of Drug Abuse Neurons Nucleus Accumbens Odors Outcome Policies Predictive Value Prevalence Procedures Process Psychological reinforcement Public Health Rattus Reporting Research Resources Response to stimulus physiology Rewards Sampling Self Administration Self-Administered Side Signal Transduction Stimulus System Task Performances Testing Time Work addiction cingulate cortex cocaine exposure cocaine use dopamine system dopaminergic neuron effective therapy executive function expectation experimental study improved innovation insight neural correlate neuromechanism neurotransmission optogenetics relating to nervous system repaired response restoration

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 function in brain circuits critical for computations of reward predictions and action policies. `Reward prediction' signals reflect the reward the animal expects to receive as a result of behavior, thus reflecting goals associated with decisions. `Action policies' are rules that govern behavior that at 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 and outcomes/responses. `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 an odor 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) encodes 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 (e.g., in this context bias choices to the right). 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, our work has shown that firing in anterior cingulate cortex (ACC) better reflects an integrated unsigned reward prediction error signal, increasing during unexpected up- and down-shifts in value at the time of the error and during cue sampling on subsequent trials. This work suggests a model by which DA reward prediction errors modify reward prediction signals in NAc and action policy signals in DLS, while ACC increases attention toward stimuli after violations in reward prediction (signaled by DA) so that learning can occur. Cocaine exposure impairs reward prediction signals and prediction error signals in NAc and DA neurons, while increasing the prevalence of contextual action policies in DLS. In Aim 1 we propose to restore the cocaine induced imbalance of processing between NAc and DLS by repairing DA signals via optogenetics. In Aim 2 we will determine if attention and error correlates in ACC are altered after cocaine exposure. Finally, in Aim 3, we will determine how ACC and DA neurons interact during the computation of errors and the development of cue selectivity. 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 might restore behavior and neural constructs in downstream regions to normal levels.

项目总结