Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation.
Separate orexigenic hippocampal ensembles shape dietary choice by enhancing contextual memory and motivation.
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单独的食欲海马体通过增强情境记忆和动机来塑造饮食选择。
DOI：
10.1101/2023.10.09.561580
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
deLartigue,Guillaume
中科院分区：
文献类型：
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作者：
Yang,Mingxin;Singh,Arashdeep;McDougle,Molly;Décarie-Spain,Léa;Kanoski,Scott;deLartigue,Guillaume
海马体（HPC）已经成为控制食物摄入的关键角色，超越了其在记忆中的众所周知的作用。虽然之前的研究主要将HPC与食物摄入抑制联系起来，但最近的研究表明它在食欲过程中发挥作用。在这里，我们确定了空间上不同的神经元群体内的背HPC（dHPC），无论是脂肪或糖，有效的天然脂肪酸，有助于肥胖的发展。使用活性依赖的营养响应dHPC神经元的遗传捕获，我们证明了两个群体通过不同的机制在促进营养素特异性摄入方面的因果作用。糖反应神经元编码糖位置的空间记忆，而脂肪反应神经元选择性地增强脂肪摄入的偏好和动机。重要的是，刺激营养反应性dHPC神经元增加了食物摄入，而消融差异影响致肥胖饮食消费并防止饮食诱导的体重增加。总的来说，这些发现揭示了以前未知的促食欲回路，这些回路是宏量营养素特定消耗的基础，并为开发潜在的肥胖治疗方法提供了基础。
The hippocampus (HPC) has emerged as a critical player in the control of food intake, beyond its well-known role in memory. While previous studies have primarily associated the HPC with food intake inhibition, recent research suggests a role in appetitive processes. Here we identified spatially distinct neuronal populations within the dorsal HPC (dHPC) that respond to either fats or sugars, potent natural reinforcers that contribute to obesity development. Using activity-dependent genetic capture of nutrient-responsive dHPC neurons, we demonstrate a causal role of both populations in promoting nutrient-specific intake through different mechanisms. Sugar-responsive neurons encoded spatial memory for sugar location, whereas fat-responsive neurons selectively enhanced the preference and motivation for fat intake. Importantly, stimulation of either nutrient-responsive dHPC neurons increased food intake, while ablation differentially impacted obesogenic diet consumption and prevented diet-induced weight gain. Collectively, these findings uncover previously unknown orexigenic circuits underlying macronutrient-specific consumption and provide a foundation for developing potential obesity treatments.