Metabolic state dependence of olfactory cortex flavor representation during hedonic overeating

肥胖是西方社会的一个核心公共健康问题。一个潜在的问题是，在享乐性暴饮暴食期间，机体的热量摄入和代谢需求不耦合。享乐性暴饮暴食会升级为暴饮暴食的症状。调节代谢需求和热量摄入反馈回路的一个因素是对味道的感官感知。嗅觉是味觉的重要组成部分，对食物的享乐性评价有重要影响。然而，目前尚不清楚从享乐性暴饮暴食到暴饮暴食的转变是如何通过嗅觉反应反映出来的。因此，本研究旨在了解嗅觉知觉与暴饮暴食之间的关系。梨状皮质（PCx）是大脑皮层嗅觉处理的第一个阶段，在此生成合成气味图像并识别气味。在这里，我们将分析前PCx的多模态风味反应。我们想了解暴饮暴食过程中不同特定前PCx （aPCx）回路的味觉表征与不同代谢状态下饱腹感之间的关系。主要的潜在问题是，食物的摄入量是否受到感官知觉的调节。我们还想进一步验证这样一个假设，即暴饮暴食和诱导肥胖的饮食会改变aPCx对味道的感官表征。该建议需要结合清醒自由运动小鼠神经元活动的体内钙成像和行为任务。这项行为任务旨在量化高享乐价值食物的消费，并在成像过程中实时升级暴饮暴食。对于清醒自由运动小鼠侧腹侧aPCx的体内成像，显微内镜透镜将与头戴式小型化显微镜相结合。转基因方法将允许基因编码钙指标（GECIs）的细胞类型特异性表达。首先，我们将分析不同代谢状态下aPCx在暴食诱导过程中风味表征的电路特异性变化。然后，我们将测试嗅觉感知的实验操作对饮食摄入和风味表征的影响。最后，我们想要评估在肥胖诱导饮食的不同时间点aPCX风味表征的动态变化。通过这项研究计划，我们将对理解饮食失调行为的感官基础做出重大贡献。

Obesity is a central public health issue in western society. An underlying problem is the uncoupling of caloric intake and metabolic needs of the organism during hedonic overeating. Hedonic overeating can escalate into the symptom of binge eating. One factor that modulates the feedback loop of metabolic need and caloric intake is the sensory perception of flavors. Olfaction is a critical part of flavor perception and significantly influences the hedonic evaluation food items. However, it is unclear how adaptations related to the transition from hedonic overeating to binge eating are reflected by the olfactory flavor response. This proposal therefore aims to understand the relationship between olfactory sensory perception and binge eating. The piriform cortex (PCx) is the first cortical olfactory processing stage where synthetic odor images are generated and odors are identified. Here, we will analyse the multimodal flavor response in the anterior PCx. We want to understand the relationship between the sensory representation of flavors during binge eating in different specific anterior PCx (aPCx) circuits and satiation at different metabolic states. The main underlying question is whether the amount of food consumption is modulated by sensory perception. We further want to test the hypothesis that the escalcation of binge eating and an obesity inducing diet will alter the sensory representation of flavors in the aPCx. The proposal requires the combination of in-vivo calcium imaging of neuronal activity in awake freely moving mice and a behavioral task. The behavioral task is designed to quantify consumption of high hedonic value food and escalate binge eating in real time during imaging sessions. For in vivo imaging of the lateroventral aPCx in awake freely-moving mice, microendoscopic lenses will be combined with a head-mounted, miniaturized microscope. Transgenic approaches will permit for cell-type specific expression of genetically encoded calcium indicators (GECIs). In a first step, we will analyze the circuit-specific changes of flavor representation in the aPCx during binge eating induction under different metabolic states. We will then test the effects of experimental manipulations of olfactory perception on dietary intake and flavor representation. Finally, we want to assess the changes in the dynamics of aPCX flavor representation during different time points of an obesity inducing diet. With this research proposal, we will make a significant contribution towards an understanding of the sensory underpinnings of dysregulated eating behavior.