Midbrain Neural Circuit Elements That Underlie Cue-Reward Associations

提示奖励关联背后的中脑神经回路元件

• 批准号: 8803135
• 负责人: Garret D Stuber
• 金额: $ 9.86万
• 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: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8803135
• 关键词: Association Learning; Automobile Driving; Behavioral; Brain; Brain region; Cations; Cell Nucleus; Cells; Chloride Ion; Chlorides; Conditioned Stimulus; Cues; Development; Diagnosis; Disease; Dopamine; Drug Addiction; Electrodes; Elements; Extinction (Psychology); Fiber; Future; Glutamates; Goals; Habenula; Halorhodopsins; Hypothalamic structure; Implant; In Vitro; Incentives; Indium; Inherited; Lateral; Light; Mediating; Mental disorders; Midbrain structure; Monitor; Mus; Neurons; Nucleus Accumbens; Optics; Outcome; Output; Pathway interactions; Play; Population; Probability; Process; Pump; Research; Rewards; Role; Signal Transduction; Slice; Societies; Stimulus; Substance abuse problem; Substantia nigra structure; Sucrose; Synapses; Synaptic Transmission; Testing; Training; Ventral Tegmental Area; addiction; approach behavior; conditioning; dopaminergic neuron; improved; in vivo; innovation; light gated; motivated behavior; nervous system disorder; neural circuit; neuromechanism; neuropsychiatry; neurotransmitter release; new therapeutic target; novel; optical fiber; optogenetics; patch clamp; postsynaptic; presynaptic; research study; response

DESCRIPTION (provided by applicant): Utilizing environmental information to predict future positive and negative outcomes is a behavioral adaptation that is essential for survival. While this process is required for the control of natural motivated behavioral responding to obtain rewards, the neural circuits that encode cue-reward associations are thought to be dysfunctional in neuropsychiatric disorders such as addiction. Therefore, it is essential that further research is conducted to delineate the neural mechanism that underlie responses to reward-predictive cues in an effort to uncover specific neural circuit elements that mediate this phenomena. Signaling by midbrain dopamine neurons is thought to play an important role in controlling the formation and expression of cue-induced reward seeking. In this proposal, we aim to study neural circuit elements within the ventral midbrain that may be important for activating or inhibiting dopaminergic function and therefore influence the acquisition and expression of cue-reward associations. To accomplish this, we will take a multifaceted approach. We will perform in vitro slice electrophysiological experiments to characterize the functional connectivity between specific excitatory inputs to dopaminergic and GABAergic neurons within the midbrain. In addition, we will use in vivo optogenetic stimulation/inhibition experiments to establish or refute causal relationships between genetically and anatomically defined neural circuit elements in the midbrain and the release of dopamine in the nucleus accumbens to reward-predictive cues. The information gained from these studies may greatly advance our understanding of the neural circuits that encode cue-reward associations.

描述（由申请人提供）：利用环境信息来预测未来的积极和消极结果是一种对生存至关重要的行为适应。虽然这一过程是控制自然动机行为反应以获得奖励所必需的，但编码线索-奖励关联的神经回路被认为在神经精神疾病（如成瘾）中功能失调。因此，有必要进行进一步的研究，以描绘奖励预测线索的反应背后的神经机制，以揭示介导这种现象的特定神经回路元件。中脑多巴胺神经元的信号传导被认为在控制线索诱导的奖赏寻求的形成和表达中起重要作用。在这个提议中，我们的目标是研究腹侧中脑内的神经回路元件，这些元件可能对激活或抑制多巴胺能功能很重要，因此会影响线索奖励关联的获得和表达。为了实现这一目标，我们将采取多方面的方法。我们将进行体外切片电生理实验，以表征中脑内多巴胺能和GABA能神经元的特异性兴奋性输入之间的功能连接。此外，我们将使用体内光遗传学刺激/抑制实验来建立或反驳中脑中遗传学和解剖学定义的神经回路元件与多巴胺在脑桥核中释放以奖励预测线索之间的因果关系。从这些研究中获得的信息可能会极大地促进我们对编码线索奖励关联的神经回路的理解。