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

基本信息

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
项目类别：
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

项目摘要

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于生存至关重要的行为适应。虽然这个过程是控制自然动机行为反应以获得奖励所必需的，但编码提示-奖励关联的神经回路被认为在成瘾等神经精神疾病中功能失调。因此，有必要进行进一步的研究来描述对奖励预测线索做出反应的神经机制，以努力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励寻求的形成和表达中发挥着重要作用。在本提案中，我们的目标是研究腹侧中脑内的神经回路元件，这些元件对于激活或抑制多巴胺能功能可能很重要，从而影响提示奖励关联的获取和表达。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学实验，以表征中脑内多巴胺能和 GABA 能神经元的特定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和解剖学定义的神经回路元件与伏隔核中多巴胺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提示奖励关联的神经回路的理解。