Neural circuits for computing dopamine prediction errors

用于计算多巴胺预测误差的神经电路

• 批准号: 8841607
• 负责人: Neir Eshel
• 金额: $ 4.1万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-18 至 2015-09-17
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8841607
• 关键词: Agonist; Cations; Cells; Code; Cues; Dependovirus; Development; Dopamine; Electrophysiology (science); Environment; Exhibits; Goals; Health; Implant; Implanted Electrodes; Laboratories; Learning; Lesion; Light; Maps; Mental Depression; Mental disorders; Midbrain structure; Mus; Muscimol; Neurons; Odors; Outcome; Pattern; Placebo Effect; Process; Proton Pump; Psychological reinforcement; Punishment; Ramp; Rattus; Rewards; Role; Schizophrenia; Shapes; Signal Transduction; Stimulus; System; Testing; Time; Training; Update; Ventral Tegmental Area; Work; addiction; base; classical conditioning; dopamine system; dopaminergic neuron; drug reward; expectation; experience; gamma-Aminobutyric Acid; in vivo; inhibitory neuron; interdisciplinary approach; neural circuit; optogenetics; receptor; research study; resilience; response; severe mental illness; theories

As we encounter stimuli in the environment, we make predictions about their value. When outcomes fail to match these predictions, we update our predictions to reflect new experience. This learning process is thought to involve midbrain dopamine (DA) neurons, which encode prediction errors, or the difference between actual and expected reward. Besides contributing to learning, prediction errors may lie at the core of many mental illnesses, including addiction (where drug rewards are overvalued) and depression (where previously pleasurable activities no longer feel rewarding). Although much work has gone into characterizing the responses of DA neurons to reward and punishment, less is known about how DA neurons calculate these responses, and in particular, how predictions are conveyed. Recently, it was suggested that GABAergic neurons in the ventral tegmental area might relay information to neighboring DA neurons about the predicted value of cues. By sustaining activity from the onset of a reward-predicting cue to the time of expected reward, these inhibitory neurons might provide DA neurons with information they need to calculate prediction errors. This project will use optogenetics, electrophysiology, and reversible lesions to test this theory. In the first part, the inhibitory expectation signal will be eliminated on a trial-by-trial basis while the activity of DA neurons is recorded. Without the expectation signal, DA neurons should respond robustly to rewards, even when they are fully predicted. In the second part, the origin of the expectation signal will be probed through reversible inactivation of the orbitofrontal cortex (OFC). If the OFC helps drive the GABA expectation signal, then inactivating OFC should eliminate this signal in GABA cells, and cause DA neurons to respond in the same way to expected and unexpected reward. Together, these experiments will shed light on how dopamine neurons calculate prediction errors, and identify possible points of vulnerability in this system.

当我们在环境中遇到刺激时，我们会对它们的价值做出预测。当结果与预测不符时，我们会更新预测以反映新的经验。这个学习过程被认为与中脑多巴胺（DA）神经元有关，该神经元负责对预测错误或实际奖励与预期奖励之间的差异进行编码。除了有助于学习之外，预测错误可能是许多精神疾病的核心，包括成瘾（药物奖励被高估）和抑郁（以前令人愉快的活动不再有回报）。尽管已经有很多工作来描述DA神经元对奖励和惩罚的反应，但对于DA神经元如何计算这些反应，特别是如何传达预测，我们知之甚少。