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

项目摘要 学习和决策是由对未来结果的期望驱动的。三个关键参数 确定未来结果的估值是1）“多少”预期，2）“何时”预期，3） “什么”期望（即，结果预测）。然而，结果预测是如何由大脑产生的， 对预测线索的反应知之甚少。举例来说，当结果预测是所谓的 初级视觉皮层（VC）中的“奖励时间”活动，当视觉刺激被激活时， 行为条件反射延迟水奖励。此前，我们已经证明， 活动产生于VC本身，需要基底前脑胆碱能神经支配的形成。我们 也证明了这种活动可以告知视觉提示动作的时间。其实，背 纹状体（DS）是VC的直接下游运动相关靶点，在飞行员数据中也观察到其表达 这个活动。总之，这些观察结果使视觉皮质纹状体回路（VC»DS）成为一个强大的 该系统旨在解决如何通过神经学习和报告结果预测。结合我们 结果预测信号如何通过内部强化信号来学习的计算模型 VC»DS，这些观察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这个回路学习结果预测信号，以及是否 VC»DS中的预测信令通知决策行为。 食欲（Aim 1a）和厌恶（Aim 1b）条件反射是否导致视觉皮质纹状体 电路学习以产生结果预测信号是未知的，尽管导频数据指示它是未知的。测试 从我们的正式模型预测，选择性干扰抑制电路元件将评估是否VC是 向DS（Aim 1c）提供预测信令的站点。VC内胆碱能纤维的引导性Ca 2+成像表明 奖励，以及惩罚报告给VC（Aim 2a），以符合其作为教学的预期作用 信号，但提高了在DS（Aim 2b）下游学习结果效价的可能性。因此 VC内胆碱能激活的程度可能有助于教导VC表达和来源于DS信号，预测 预期结果的时间和幅度（Aim 2c），而DS可以作为一个网站，将这些 预测信号与他们适当的奖励寻求/惩罚避免行为。的能力 光遗传学模拟结果信号提供了一种手段，以测试学习的结果预测信号是否 在VC»DS通知决策：通过灌输虚构的奖励预期之上的行为条件 奖励预期的其他相等的价值，结果预测信号在VC»DS可以显示影响 未来决策（Aim3a&b）。这里所作的观察将促进对 在许多认知疾病中受损的感觉信息的行为意义是如何 学习是为了记住过去的经验并为决策提供信息。

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.