Metabolic state dependence of olfactory cortex flavor representation during hedonic overeating

在西方社会，肥胖是一个核心的公共卫生问题。一个潜在的问题是，在享乐主义过量进食期间，机体的卡路里摄入量和代谢需求脱钩。享乐主义的暴饮暴食会升级为暴饮暴食的症状。调节新陈代谢需求和卡路里摄入量的反馈循环的一个因素是对味道的感觉。嗅觉是食品风味感知的重要组成部分，对食品的享乐性评价有重要影响。然而，目前还不清楚从享乐主义暴饮暴食到暴饮暴食的适应是如何通过嗅觉味道反应来反映的。因此，这项建议旨在了解嗅觉知觉和暴饮暴食之间的关系。梨状皮质(PCX)是皮质嗅觉处理的第一个阶段，在这里产生合成气味图像并识别气味。在这里，我们将分析前PCX的多峰味道反应。我们想要了解暴饮暴食时不同特定的前PCx(APCx)环路中味道的感觉表征与不同代谢状态下的饱腹感之间的关系。主要的潜在问题是，食物的消耗量是否受感官知觉的影响。我们还想进一步检验这一假设，即暴饮暴食和导致肥胖的饮食将改变APCX中味道的感官表现。该提案要求将清醒自由活动小鼠神经元活动的体内钙成像与行为任务相结合。这项行为任务旨在量化高享乐价值食物的摄入量，并在成像过程中实时升级暴饮暴食。为了对清醒自由活动的小鼠的侧腹侧APCx进行活体成像，显微内窥镜将与头戴式微型显微镜相结合。转基因方法将允许特定细胞类型表达遗传编码的钙指示物(GECI)。在第一步中，我们将分析在不同代谢状态下暴饮暴食诱导过程中APCx中风味表征的电路特异性变化。然后，我们将测试嗅觉的实验操作对饮食摄入量和味道表现的影响。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。有了这项研究建议，我们将为理解失调饮食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.