Hunger And Thirst Guided Decision Making Via Hippocampal Encoding Of Internal State

为了生存，动物必须采取行动来满足它们的核心生理需求。例如，当动物饥饿时，它必须改变行为，以增加找到食物的可能性。同样，当口渴时，它必须增加找到水的可能性。行为目标的这种灵活和动态变化对于正确规划摄食行为至关重要，它们的功能障碍被认为是肥胖和厌食症等疾病的主要因素。这种行为的关键是能够理解与环境中的行为或提示相关的结果通常取决于您的内部状态。因此，人们经常提出，内部状态可以充当背景--根据动物是饥饿还是口渴，可以有区别地学习适当的行为。然而，饥饿和口渴的外围信号如何整合到更广泛的神经回路的背景规划和决策至关重要的支持这种灵活的目标导向的behaviors.In本提案中，我们将调查的假设，腹侧海马-一个关键区域的背景学习-是至关重要的，让灵活的行为由内部状态的指导。我们将使用最先进的成像，电生理学和光遗传学的组合，直接在突触，细胞和电路水平上研究饥饿和口渴信息如何在海马体中表达，以及这些信息如何用于指导内部状态相关的决策。我们的首要目标是提供一个分子到电路到行为描述如何利用外围信号中的内部状态信息来指导决策行为。我们的目标是，这项研究将提供一个机制框架，以了解这些过程如何在饮食失调的临床前模型中失败，并为这些疾病提供更有效的治疗方法。

In order to survive, animals must act to address their core physiological needs. For example, when an animal is hungry, it must alter its behaviour in order to increase the likelihood of finding food. Similarly, when thirsty, it must increase the likelihood of finding water. Such flexible and dynamic changes to behavioural goals are crucial for correct planning of ingestive behaviour, and their dysfunction is thought to be a major factor in disorders such as obesity and anorexia.Key to such behaviour is the ability to understand that the outcome associated with an action or cue in the environment is often different dependent on your internal state. As a result, it is often proposed that internal state can act as a context - where appropriate behaviour can be learnt differentially, dependent on whether the animal is hungry or thirsty. However, how peripheral signals of hunger and thirst are integrated into the wider neural circuits essential for contextual planning and decision making - crucial to support such flexible goal directed behaviour - remains unclear.In this proposal we will investigate the hypothesis that the ventral hippocampus - an area key for contextual learning - is crucial to allow flexible behaviour guided by internal state. We will use a combination of state-of-the-art imaging, electrophysiology and optogenetics to directly investigate at the synaptic, cellular and circuit level how hunger and thirst information are represented in the hippocampus, and how this information is used to guide internal state dependent decision making.Our overarching aim is to provide a molecules-to-circuits-to-behaviour description of how internal state information signalled in the periphery can be utilised to guide decision-making behaviour. Our goal is that this research will provide a mechanistic framework to understand how these processes fail in preclinical models of eating disorders, and provide avenues to more effective treatments for these disorders.