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预期驱动的。三个关键参数 决定未来结果的估值是1)预期多少，2)何时预期，以及3) 期待什么(例如，结果预测)。然而，结果预测是如何由大脑在 人们对预测性线索的反应知之甚少。举例说明结果预测的时间是所谓的 初级视觉皮质(VC)的“奖赏计时”活动，当视觉刺激被 在行为上受到延迟的水奖励的制约。此前，我们已经证明了这一时机 活动是在VC内部产生的，需要形成基底前脑胆碱能神经支配。我们 还证明了这一活动对视觉提示动作的时间有影响。事实上，背部 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它表达 这项活动。综上所述，这些观察使视觉皮质纹状体回路(VC？DS)成为一种强大的 系统，以解决如何学习和报告结果预测神经。结合我们的 结果预测信号如何通过强化信号学习的计算模型 这些观察结果很好地激励了我们研究VC？DS电路是如何产生结果预测的 信号，胆碱能信号如何教这个电路学习结果预测信号，以及 VC？DS中的预测性信号为决策行为提供信息。 食欲(Aim1a)和厌恶(Aim1b)条件反射是否导致视觉皮质纹状体 电路学习产生结果预测信号是未知的，尽管试点数据表明是这样的。测试 来自我们正式模型的预测，选择性地扰动抑制电路元件将评估VC是否 向DS(Aim1c)提供预测信号的站点。飞行员对VC内胆碱能纤维的钙成像表明 这种奖励和惩罚被报告给风险投资(Aim2a)，以符合其所谓的教学角色 信号，但增加了结果价在DS(Aim2b)下游学习的可能性。因此， Vc内胆碱能激活的程度可能有助于教Vc表达和来源DS信号预测 预期结果的时间和大小(Aim2c)，而DS可以作为关联这些结果的站点 具有适当的奖惩行为的预测性信号。有能力 光遗传学模拟结果信号提供了一种测试获得性结果预测信号是否 在VC中，DS为决策提供信息：通过在行为条件化之上灌输虚构的回报期望 其他相同价值的奖励期望，VC？DS中的结果预测信号可以显示为影响 未来决策(Aim3a和b)。在这里所做的观察将促进对 在许多认知疾病中受损的感觉信息的行为意义如何的机制 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.