Top-down regulation of compulsive reward-seeking behavior by medial prefrontal cortex

内侧前额叶皮层对强迫性寻求奖励行为的自上而下调节

• 批准号: 9123317
• 负责人: Christina Kim
• 金额: $ 3.47万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9123317
• 关键词: Address; Behavior; Behavioral; Behavioral Mechanisms; Brain region; Calcium; Country; Dopamine D2 Receptor; Down-Regulation; Electrophysiology (science); Equilibrium; Fiber; Future; Image; Lateral; Lead; Left; Medial; Mus; Neural Pathways; Neurons; Nucleus Accumbens; Pathway interactions; Pattern; Photometry; Population; Population Dynamics; Prefrontal Cortex; Process; Rabies; Rewards; Self Stimulation; Shock; Signal Transduction; Substance Addiction; Substance abuse problem; Synapses; Testing; Therapeutic; Time; Training; Ventral Tegmental Area; Water; Work; addiction; awake; brain pathway; cell type; cost; dopaminergic neuron; executive function; experience; foot; hippocampal pyramidal neuron; in vivo; insight; lens; neural circuit; novel; optogenetics; public health relevance; relating to nervous system; research study; response; trait

 DESCRIPTION (provided by applicant): While the drive to seek reward is a fundamental trait shared across many species, when left unchecked it can lead to addiction and substance abuse. A potential therapeutic approach to treating addiction could be to reset the balance between the neural circuits that drive and suppress reward-seeking. To achieve such an approach, we must characterize the specific neural state changes that occur with compulsive reward-seeking, and identify the neural pathways that can reverse this behavior. This proposal aims to use 2photon imaging to reveal the neural activity patterns in the nucleus accumbens (NAc) during a type of compulsive reward-seeking behavior, optogenetic self-stimulation of the ventral tegmental area dopamine neurons. This will reveal the changes in neural dynamics that emerge with repeated, compulsive reward-seeking which underlies addiction. In addition, this proposal will test whether medial prefrontal cortex (mPFC) stimulation is able to exert regulatory action to reduce compulsive reward-seeking by altering the neural activity patterns that are observed in NAc. Finally, this proposal aims to identify which specific mPFC projection neurons drive suppression of reward-seeking behaviors using cell type-specific rabies GCaMP6 and fiber photometry imaging. The findings from this proposed project will provide a novel insight into how NAc circuit dynamics become altered during addiction, and how these changes may be counteracted by top-down executive control from the mPFC.