Role of the orbitofrontal cortex in learning of goal-directed action

人类和动物以适应性的方式选择和执行先前学习的行为，以获得特定的目标，如食物，这是在不断变化的环境中生存所必需的能力。神经科学的一个基本挑战是理解决策过程的神经基础，这些决策过程是目标导向行动的选择和表现的基础。例如，为了做出适应性决策，不仅必须检索有关行为及其后果之间的学习关系的信息。还必须评估一项行动的预期价值或收益是否值得忍受为获得它而付出的努力或成本，并分析当前的情境因素，如动机状态（例如饥饿）。因此，在决定选择哪种行动方针之前，必须权衡现有应对方案的实际成本和效益。我们最近的数据表明，内侧眶额皮质（mOFC）是关键支持这些过程的神经网络的关键组成部分。然而，mOFC的具体参与以及它与底层神经网络的其他关键组成部分的相互作用，到目前为止，在很大程度上是未知的。在这个项目中，我们将结合联合收割机药理学，光遗传学和神经回路分析方法，以检查mOFC的作用和连接mOFC与大鼠进行复杂的认知任务，允许动作选择的行为过程的详细分析的神经网络的通路。这项研究将通过评估相关脑区神经元活动的分子标志物来补充。我们的目标是提供一个详细的描述mOFC如何有助于选择和执行目标导向的行动，并强调功能的相互作用与核的脑桥，一个已知的关键组成部分的基础神经网络，在分子，神经和行为水平。这项研究可能使重要的新的见解mOFC在决策中的确切作用仍然是难以捉摸的。我们的研究结果也可能为更深入地了解伴有前额叶功能障碍的神经精神疾病（如重度抑郁症）中的决策和行动选择受损铺平道路。

Humans and animals select and perform previously learned actions in adaptive ways to obtain specific goals such as food, a capacity that is essential to survive in an ever-changing environment. A fundamental challenge of neuroscience is to understand the neural basis of decision making processes underlying selection and performance of goal-directed action. For instance, to make adaptive decisions, it is not only vital to retrieve information about learned relationships between actions and their consequences. It is also necessary to evaluate whether the expected value or benefits of an action make it worth tolerating the efforts or costs to obtain it and to analyze current situational factors such as motivational states (e.g. hunger). Thus, actual costs and benefits of the available response options must be weighed before deciding which course of action to choose. Our recent data suggest that the medial orbitofrontal cortex (mOFC) is a key component of a neural network that critically supports such processes. However, the specific involvement of the mOFC as well as its interactions with other key components of the underlying neural network is, as yet, largely unknown. In this project, we will combine pharmacological, optogenetic and neural circuit analysis methods to examine the role of the mOFC and pathways linking the mOFC with the nucleus accumbens in rats performing complex cognitive tasks that allow for a detailed analysis of behavioral processes underlying action selection. This research will be complemented by an assessment of molecular markers of neuronal activity in involved brain areas. Our goal is to provide a detailed description of how the mOFC contributes to selection and performance of goal-directed action and highlight functional interactions with the nucleus accumbens, a known key component of the underlying neural network, on a molecular, neural and behavioral level. This research possibly allows important new insights into the exact role of the mOFC in decision making which is still elusive. Our findings could also pave the way for a deeper understanding of impaired decision making and action selection in neuropsychiatric disorders with prefrontal dysfunction such as major depression.