The production, learning, and behavioral significance of outcome prediction signaling in the corticostriatal circuit

皮质纹状体回路中结果预测信号的产生、学习和行为意义

• 批准号: 10027816
• 负责人: Marshall Gilmer Shuler
• 金额: $ 59.56万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10027816
• 关键词: Address; Affect; Animals; Behavior; Behavioral; Biological Models; Brain; Choice Behavior; Cholinergic Fibers; Cognition Disorders; Computer Models; Corpus striatum structure; Cues; Data; Decision Making; Desire for food; Dimensions; Dopamine; Dorsal; Educational process of instructing; Electrophysiology (science); Elements; Event; Fiber; Future; Goals; Human; Image; Impairment; Learning; Measures; Modeling; Motor; Neuromodulator; Neurons; Operant Conditioning; Outcome; Production; Psychological reinforcement; Punishment; Reporting; Research; Rewards; Role; Sensory; Signal Transduction; Site; Source; System; Testing; Time; Visual; Visual Cortex; Water; Work; area striata; basal forebrain; base; cholinergic; conditioning; expectation; experience; fictional works; functional outcomes; learning outcome; nerve supply; neural circuit; neuroregulation; optical sensor; optogenetics; outcome prediction; relating to nervous system; response; reward expectancy; theories; visual learning; visual stimulus

Project Summary Learning and decision-making are driven by expectations of future outcomes. Three key parameters determining the valuation of future outcomes are 1) “how much” to expect, 2) “when” to expect it, and 3) “what” to expect (ie, Outcome Prediction). However, how outcome prediction is generated by the brain in response to predictive cues is poorly understood. Exemplifying the when of outcome-prediction is so-called “reward timing” activity in the primary visual cortex (VC), which emerges in VC when visual stimuli are behaviorally conditioned with delayed water reward. Previously, we have demonstrated that this timing activity is generated within VC itself and requires basal forebrain cholinergic innervation to be formed. We have also demonstrated that this activity informs on the timing of visually-cued actions. Indeed, the dorsal striatum (DS) is VC's direct downstream motor-related target, and it is also observed in pilot data to expresses this activity. Together, these observations make the visual corticostriatal circuit (VC»DS) a powerful system to address how outcome prediction can be learned and reported neurally. Combined with our computational model of how outcome prediction signaling could be learned by reinforcement signaling within VC»DS, these observations well motivate our research into how VC»DS circuitry produces outcome prediction signals, how cholinergic signaling teaches this circuit to learn outcome predictive signaling, and whether predictive signaling in VC»DS informs decision-making behavior. Whether appetitive (Aim1a) and aversive (Aim1b) conditioning leads to the visual corticostriatal circuit learning to produce outcome prediction signals is unknown, though pilot data indicates it is. Testing predictions from our formal model, selectively perturbing inhibitory circuit elements will assess whether VC is a site sourcing predictive signaling to DS (Aim1c). Pilot Ca2+ imaging of cholinergic fibers within VC indicates that reward, as well as punishment is reported to VC (Aim2a) in keeping with its purported role as a teaching signal, but raising the possibility that outcome valence is learned downstream in DS (Aim2b). Therefore, the degree of cholinergic activation within VC may serve to teach VC to express and source to DS signals predicting the time and magnitude of expected outcomes (Aim2c), while DS may serve as a site associating those predictive signals with their appropriate reward-seeking/punishment avoiding behaviors. The ability to optogenetically mimic outcome signaling affords a means to test whether learned outcome prediction signaling in VC»DS informs decision-making: By instilling fictive reward expectancies atop behaviorally conditioned reward expectancies of otherwise equal value, outcome prediction signaling in VC»DS can be shown to impact future decision making (Aim3a&b). Observations made here will advance an understanding of the mechanisms—impaired in many cognitive diseases—of how the behavioral meaning of sensory information is learned in order to remember past experiences and inform decision making.

项目摘要 学习和决策是由对未来结果的期望所驱动的。三个关键参数 确定未来结果的价值是1）“多少”，2）“何时”，以及3） “什么”期望（即结果预测）。但是，大脑中如何产生结果预测 对预测提示的响应知之甚少。示例结果预测是所谓的 主要视觉皮层（VC）中的“奖励时机”活动，当视觉刺激为时在VC中出现 在行为上以延迟的水奖励条件。以前，我们已经证明了这个时机 活性是在VC本身中产生的，需要形成基本的前脑胆碱能神经。我们 还证明了这项活动有关视觉措施动作的时机的信息。确实，背 纹状体（DS）是VC的直接下游电动机相关目标，并且在Pilot数据中也观察到以表达 这项活动。这些观察结果使视觉皮质纹状体电路（VC»ds）成为强大的 解决如何在神经上学习和报告结果预测的系统。结合我们 通过强化信号传导可以学习结果预测信号传导的计算模型 VC»ds，这些观察结果很好地激发了我们对VC»ds电路如何产生结果预测的研究 信号，胆碱能信号如何教导该电路学习结果预测信号，以及是否是否 VC»ds中的预测信号传导为决策行为提供了信息。 食欲（AIM1A）和厌恶（AIM1B）条件是否导致视觉皮质纹状体 尽管Pilot数据表明是，但尚不清楚产生结果预测信号的电路学习。测试 我们正式模型的预测，有选择地扰动抑制电路元素将评估VC是否为 对DS的站点采购预测信号（AIM1C）。 VC内的胆碱能纤维的PILOT CA2+成像表明 该奖励以及惩罚向VC（AIM2A）报告，符合其所谓的教学角色 信号，但提高了DS（AIM2B）下游学习结果价的可能性。因此， VC内的胆碱能激活程度可能有助于教导VC表达并源用于DS信号预测 预期结果的时间和幅度（AIM2C），而DS可以用作将这些结合的网站 预测信号及其适当的寻求奖励/惩罚避免行为。能力 光源模拟的结果信号提供了一种测试学习结果预测信号的手段 在VC»ds中为决策提供了信息：通过在行为条件下灌输虚构的奖励期望 奖励对其他相同价值的奖励期望，可以证明VC»d中的结果预测信号传导会影响 未来的决策（AIM3A＆B）。在这里进行的观察将使人们对 机制 - 在许多认知疾病中受损 - 感官信息的行为含义如何 为了记住过去的经验并为决策提供信息。