The role of accumbens neural activity and dopamine release in flexible behavior

伏隔核神经活动和多巴胺释放在灵活行为中的作用

• 批准号: 8914958
• 负责人: Elizabeth A West
• 金额: $ 5.6万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8914958
• 关键词: Access to Information; Addictive Behavior; Address; Amygdaloid structure; Animals; Association Learning; Behavior; Behavioral; Brain; Chronic; Cocaine; Cognitive; Cues; Decision Making; Disease; Dopamine; Dopamine Receptor; Drug Addiction; Environment; Exposure to; Food; Goals; Impairment; Individual; Learning; Lesion; Link; Measures; Methods; Motor; Neurobiology; Neurons; Nucleus Accumbens; Outcome; Output; Patients; Performance; Play; Process; Rattus; Recording of previous events; Relative (related person); Rewards; Role; Satiation; Scanning; Selection Bias; Signal Transduction; Staging; Stimulus; Structure; System; Testing; Therapeutic Intervention; Time; Training; Update; Ventral Tegmental Area; addiction; base; classical conditioning; design; dopaminergic neuron; experience; flexibility; insight; neural circuit; neurobiological mechanism; neurochemistry; neuromechanism; neuropsychiatry; optogenetics; prevent; psychostimulant; public health relevance; reinforcer; relating to nervous system; response; reward processing; tool

DESCRIPTION (provided by applicant): The ability of an animal to alter behavior in response to changes in their environment is necessary for survival. Patients with neuropsychiatric disorders, especially addictive disorders, often have difficulty with this type of behavioral flexibility. One can measure the ability of an animal to alter goal-directed behavior following a change in outcome value using a reinforcer devaluation task. In this task, animals form associations between stimuli (e.g. cue) and specific reinforcer(s) (e.g. food rewards). The reinforcer is subsequently "devalued" by selective satiation (providing the food ad libitum). Following devaluation, normal subjects adjust their responding which reflects the new "value" of the reinforcer in the absence of new associative learning. The nucleus accumbens (NAc), in conconjuction with several other brain structures (e.g., orbitofrontal cortex and basolateral amygdala), is necessary for behavioral flexibly as measured by reinforcer devaluation tasks. However, it is unknown how DA input from the ventral tegmental area (VTA) to the NAc encodes goal-directed behavior following devaluation in "real-time," or how manipulations of DA release can modulate this behavior. In order to assess this, two Specific Aims are proposed to address these issues. Aim 1 is designed to use electrochemical methods (fast scan cyclic voltammetry) to measure rapid DA signaling in the NAc core and shell to reward predictive cues and responses following reward devaluation. Aim 2 will use optogenetic manipulations to artificially stimulate DA release in NAc during acquisition or expression of the reinforcer devaluation task. Understanding the neural circuitry underlying flexible goal-directed behavior will help elucidate neural impairments in patients with neuropsychiatric disorders. As such, the proposed studies will provide critical insight into potentially new and more selective target systems for therapeutic intervention for individuals with maladaptive reward seeking, a hallmark of drug addiction.

描述（由申请人提供）：动物根据环境变化而改变行为的能力对于生存是必要的。患有神经精神疾病，尤其是成瘾性疾病的患者，通常难以保持这种行为灵活性。人们可以使用强化物贬值任务来衡量动物在结果值变化后改变目标导向行为的能力。在此任务中，动物在刺激（例如提示）和特定强化物（例如食物奖励）之间形成关联。随后，强化剂会因选择性饱足（随意提供食物）而“贬值”。贬值后，正常受试者会调整他们的反应，这反映了在缺乏新的联想学习的情况下强化物的新“价值”。伏隔核（NAc）与其他几种大脑结构（例如，眶额皮质和基底外侧杏仁核）结合，对于通过强化物贬值任务测量的灵活行为是必要的。然而，目前尚不清楚从腹侧被盖区 (VTA) 到 NAc 的 DA 输入如何编码“实时”贬值后的目标导向行为，或者如何操纵 DA 释放来调节这种行为。为了评估这一点，提出了两个具体目标来解决这些问题。目标 1 旨在使用电化学方法（快速扫描循环伏安法）测量 NAc 核心和外壳中的快速 DA 信号传导，以奖励奖励贬值后的预测线索和反应。目标 2 将使用光遗传学操作在强化物贬值任务的获取或表达过程中人为刺激 NAc 中的 DA 释放。了解灵活的目标导向行为背后的神经回路将有助于阐明神经精神疾病患者的神经损伤。因此，拟议的研究将为潜在的新的、更具选择性的目标系统提供重要的见解，用于对具有适应不良奖励寻求（吸毒成瘾的标志）的个体进行治疗干预。