Dopamine synapses and operant conditioning

多巴胺突触和操作性条件反射

• 批准号: 10515743
• 负责人: David Sulzer
• 金额: $ 2.64万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-07-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10515743
• 关键词: Action Potentials; Address; Amphetamines; Animals; Antipsychotic Agents; Attention Deficit Disorder; Attentional deficit; Axon; Behavior; Behavioral; CNR1 gene; Calcium; Cannabinoids; Chemicals; Cholinergic Receptors; Complex; Corpus striatum structure; Coupled; Cues; Data; Decision Making; Dopamine; Dopaminergic Agents; Drug abuse; Electrochemistry; Endocannabinoids; Environment; Exhibits; Future; Glutamates; Hippocampus (Brain); Image; Individual; Interneurons; Kinetics; Laboratories; Learning; Measures; Mediating; Motor; Muscarinic Acetylcholine Receptor; Neurons; Neurotransmitters; Operant Conditioning; Opioid; Optics; Organism; Output; Parkinson Disease; Pathway interactions; Periodicity; Pharmaceutical Preparations; Photons; Probability; Protocols documentation; Psychoses; Regulation; Response to stimulus physiology; Rewards; Role; Schizophrenia; Self Administration; Self Stimulation; Sensory; Signal Transduction; Site; Slice; Stimulus; Structure; Synapses; Techniques; Testing; Thalamic structure; Time; addiction; antagonist; cannabinoid receptor; cholinergic; cholinergic neuron; experience; experimental study; in vivo; learned behavior; motor learning; neural circuit; neural correlate; neuromuscular; neurotransmission; neurotransmitter release; novel; operation; postsynaptic; presynaptic; quantum; receptor; response; sensor; sensory gating; sensory stimulus; synaptic function; transmission process; voltage

Abstract: The dopaminergic (DA) synapse has been studied since the 1950s, when it was implicated in motor function, actions of antipsychotic drugs, and drug abuse. The study of DA synapses has however lagged behind that of other synapses, due to a lack of means to record dopamine release. To address this, chemical techniques have been developed, in particular electrochemical recording techniques and fluorescent false neurotransmitters (FFNs), that provide the first optical measure of neurotransmitter release from individual presynaptic sites. From these techniques, in some ways, we now know more about DA synapses than any other in the CNS. Here, we extend the contemporary understanding of DA synapses to reveal their roles in the interaction of higher organisms with the environment. This is now possible due to technical and conceptual advances, including the use of techniques novel to this proposal, including FFNs and DA-specific voltage sensors. This project tests if a) an interaction between sensory-related and reward-related excitation “gates” local DA release, and whether this is required for normal learning and behavior; b) DA filters excitation by specific interactions with cannabinoid receptors to mediate decision-making and learning, c) learned behaviors that become established “refine” synaptic circuits by selectively decreasing local DA activity, and that this enables future learning. The results of these experiments promise to indicate how addictive drugs such as amphetamine and opiates act to disrupt the normal operation of these steps.

摘要： 多巴胺能（DA）突触自20世纪50年代以来一直在研究，当时它与运动功能有关， 抗精神病药物的作用和药物滥用。然而，对DA突触的研究却落后于 由于缺乏记录多巴胺释放的手段，为了解决这个问题，化学技术 已经开发了，特别是电化学记录技术和荧光假 神经递质（FFN），其提供从个体的神经递质释放的第一光学测量。 突触前部位通过这些技术，在某些方面，我们现在对DA突触的了解比任何 另一个在CNS。在这里，我们扩展了当代对DA突触的理解，以揭示它们在大脑中的作用。 高等生物与环境的相互作用。由于技术和概念上的原因，这现在已经成为可能 进步，包括使用新的技术，这一建议，包括FFN和DA特定的电压 传感器.这个项目测试a）感觉相关和奖励相关的兴奋“门”之间的相互作用 局部DA释放，以及这是否是正常学习和行为所需的; B）DA通过以下方式过滤激发： 与大麻素受体的特异性相互作用，以介导决策和学习，c）学习行为 通过选择性地降低局部DA的活性， 使未来的学习。这些实验的结果有望表明，成瘾性药物，如 安非他明和鸦片制剂的作用是破坏这些步骤的正常操作。