The neurobiology of learning from rewards and mistakes

我研究的总体目标是了解大脑是如何做出选择的。人类和动物有巨大的能力根据经验来适应选择，但神经选择机制有时会产生不合理的结果，特别是在兴奋或压力等高度情感状态下。我的研究计划的长期愿景是发展一个神经生物学选择机制的综合理论，可以解释基于经验的选择适应和情感状态的调节。目前许多理论认为，大脑至少有两个不同的系统可以控制选择：一个“目标”系统，它使用奖励结果来快速适应选择；一个“习惯”系统慢慢适应选择。我最近在nserc资助下的研究中有了一个意想不到的突破性发现，即习惯系统可以在选择错误后驱动选择的快速适应，这与大多数流行的理论相矛盾，表明需要进行重大修正。在接下来的5年里，我的研究计划的短期目标是利用这一发现和其他最近的发现来发现神经调节剂多巴胺如何通过影响目标和习惯系统之间的动态相互作用来影响选择适应。具体来说，我的短期目标是发现多巴胺神经元的短暂爆发和暂停如何影响(1)错误后的行为选择，(2)涉及习惯和目标系统的神经结构之间的功能信号，以及(3)习惯系统中集合尖峰神经活动的稳定性和错误信息。这对于理解选择适应试错的神经机制，以及发现选择如何受到多巴胺相关情感状态（如压力和觉醒）的影响，都是至关重要的新信息。这项研究也是我未来阐明选择适应、神经信号、遗传/表观遗传调控和失调情感状态之间相互作用的关键一步。我将利用我最先进的实验室，在啮齿动物身上集成体内电生理、药理学和光遗传学技术，对多巴胺调节快速影响正在进行的神经动力学从而影响选择的机制进行广泛的定量研究。我的多学科研究项目和细胞到系统的研究方法为HQP提供了特殊的培训，并为我们在分子和系统水平上的决策理论的变革进步做好了准备，这对一系列因学习障碍和不良选择而产生的社会和经济需求有潜在的影响。此外，在这项研究中开发的先进分析工具将加速新兴技术的发展，例如我正在进行的人类功能性大脑状态检测的商业化。

The overall goal of my research is to understand how the brain makes choices. Humans and animals have a tremendous capacity to adapt choices based on experience, but neural choice mechanisms can sometimes produce irrational outcomes, particularly under heightened affective states such as arousal or stress. The long-term vision of my research program is to develop a comprehensive theory of neurobiological choice mechanisms that can account for both experience-based adaptation of choice and its modulation by affective states. Many current theories posit that the brain has at least two distinct systems that can control choice: a ‘goal’ system that uses reward outcomes to adapt choices quickly; and a ‘habit’ system that adapts choices slowly. My recent NSERC-funded work led to an unexpected breakthrough discovery that the habit system can drive rapid adaptation of choice following choice errors, which contradicts most prevailing theories and indicates that major revisions are needed. The short-term objectives of my research program over the next 5 years are to capitalize on this discovery and other recent findings to discover how the neuromodulator dopamine influences choice adaptation by influencing the dynamical interaction between goal and habit systems. Specifically, my short-term objectives are to discover how brief bursts and pauses of dopamine neurons affect (1) behavioural choice after errors, (2) functional signaling between neural structures involved in habit and goal systems, and (3) the stability and error information in ensemble spiking neural activity in the habit system. This is essential new information needed for understanding the neural mechanisms of trial-and-error choice adaptation, and for discovering how choices are influenced by dopamine-related affective states, such as stress and arousal. This research is also a key step for my future objectives of elucidating reciprocal interactions between choice adaptation, neural signaling, genetic/epigenetic regulation, and dysregulated affective states. I will leverage my state-of-the-art laboratory for integrated in vivo electrophysiological, pharmacological, and optogenetic techniques in rodents to undertake an extensive quantitative investigation of the mechanisms by which dopamine modulation rapidly affects ongoing neural dynamics to influence choice. My multidisciplinary research program and cell-to-systems research approach provides exceptional training for HQP, and is poised for transformative advances in our theory of decision-making at both molecular and systems levels, which has potential impact on a range of societal and economic needs stemming from impaired learning and poor choices. Moreover, the advanced analytical tools developed in this research will accelerate emerging technology, such as my ongoing commercialization of functional brain state detection in humans.