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

通过内部状态的海马编码，饥饿和口渴引导决策

• 批准号: EP/Y034724/1
• 负责人: Andrew MacAskill
• 金额: $ 266.23万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY034724%2F1
• 关键词: Hunger; Thirst; Guided; Decision; Making

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.

为了生存，动物必须采取行动来满足其核心生理需求。例如，当动物饥饿时，它必须改变其行为以增加找到食物的可能性。同样，当口渴时，它必然会增加找到水的可能性。行为目标的这种灵活和动态的变化对于正确规划摄入行为至关重要，并且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摄入行为相关的结果。环境中的动作或提示通常会根据您的内部状态而有所不同。因此，人们经常提出，内部状态可以充当上下文——根据动物是否饥饿或口渴，可以差异地学习适当的行为。然而，饥饿和口渴的外周信号如何整合到对情境规划和决策至关重要的更广泛的神经回路中（对于支持这种灵活的目标导向行为至关重要）仍不清楚。在本提案中，我们将研究腹侧海马体的假设情境学习的关键区域 - 对于允许内部状态引导灵活的行为至关重要。我们将结合最先进的成像、电生理学和光遗传学，在突触、细胞和电路层面直接研究饥饿和口渴信息如何在海马体中表达，以及如何利用这些信息来指导内部状态我们的首要目标是提供从分子到电路到行为的描述，说明如何利用外围发出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，并为这些疾病的更有效治疗提供途径。