Factors that govern the role of dopamine in striatal AMPAR plasticity

控制多巴胺在纹状体 AMPAR 可塑性中的作用的因素

• 批准号: 8600249
• 负责人: Mark John Thomas
• 金额: $ 19万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8600249
• 关键词: Address; Amygdaloid structure; Animals; Brain; Characteristics; Chemosensitization; Cognition; Complement; Complex; Corpus striatum structure; Data; Disease; Dopamine; Dopamine Receptor; Drug Addiction; Electrophysiology (science); Excision; Exposure to; Glutamates; Goals; Health; Heterogeneity; Hippocampus (Brain); Home environment; Hour; Incentives; Knowledge; Learning; Long-Term Potentiation; Measures; Mediating; Mental Depression; Molecular; Motivation; Mus; Neuromodulator; Neurons; Neurotransmitters; Nucleus Accumbens; Parkinson Disease; Pilot Projects; Play; Preparation; Property; Psychological reinforcement; Publishing; Receptor Activation; Recording of previous events; Relative (related person); Reporting; Rewards; Role; Schizophrenia; Signal Transduction; Slice; Specificity; Stimulus; Synapses; Synaptic Transmission; Synaptic plasticity; Testing; Tetanus; Time; Variant; cell type; experience; improved; in vivo; interest; motor control; neural circuit; neurotransmission; novel; public health relevance; relating to nervous system; research study; synaptic depression

DESCRIPTION (provided by applicant): Dopamine (DA) is a critical neuromodulator in neural circuits for motor control, cognition and reward. A chief target of DA modulation is signaling of the excitatory neurotransmitter, glutamate. What are the basic principles for DA modulation of glutamatergic signaling and plasticity? Data addressing this question are maddeningly complex. Much of this complexity may be due to variations between cell types and circuits in which DA has been studied. What other factors might contribute to the heterogeneity? Using an ex vivo brain slice preparation of the nucleus accumbens (NAc)-a central component of the neural reward circuit-our pilot studies provide evidence for two additional factors: 1) in vivo exposure t novel stimuli and 2) the timing of DA signaling in relation to long-term potentiation (LTP) induction. We find that a brief exposure to novelty enables DA to induce a long-lasting depression in NAc AMPAR synaptic strength. We also find that prior DA signaling boosts the ability of tetanic stimulation to induce robust LTP. Using direct and sensitive electrophysiologica measures, we will investigate the roles for novelty and timing in DA modulation of NAc AMPARs. We expect our studies to inform new guiding principles for dopamine modulation in health and disease.

描述（由申请人提供）：多巴胺（DA）是运动控制、认知和奖励神经回路中的关键神经调节剂。 DA 调节的主要目标是兴奋性神经递质谷氨酸的信号传导。 DA 调节谷氨酸信号和可塑性的基本原理是什么？解决这个问题的数据极其复杂。这种复杂性很大程度上可能是由于细胞类型和研究 DA 的电路之间的差异造成的。还有哪些其他因素可能导致异质性？使用伏隔核（NAc）（神经奖励回路的核心组成部分）的离体脑切片制备，我们的初步研究为两个额外因素提供了证据：1）体内暴露新刺激和2）与长时程增强（LTP）诱导相关的DA信号传导的时间。我们发现短暂接触新奇事物可以使 DA 诱导 NAc AMPAR 突触强度的持久抑制。我们还发现，先前的 DA 信号传导增强了强直刺激诱导强 LTP 的能力。使用直接和敏感的电生理学测量，我们将研究 NAc AMPAR 的 DA 调节中的新颖性和时间安排的作用。我们希望我们的研究能够为健康和疾病中多巴胺调节提供新的指导原则。