Unraveling the brain mechanisms behind how cognitive and physical stimulation dampens food cravings and food consumption in mice

在某些个体中，线索暴露会引发食物渴望，从而导致暴饮暴食和肥胖。许多研究已经研究了大脑如何触发对暗示的反应，并促进食物的寻找和消费。然而，线索反应性研究的一个重要方面是大脑如何利用反渴望机制来抑制食物寻找和消费。有趣的是，我们在老鼠身上观察到，短暂暴露在环境丰富的(EE)住房中，通过玩具和锻炼提供认知和身体刺激，可以减少线索触发的食物寻找和食物消耗。因此，EE降低了食物暗示和食物的动机影响。在我们由BBSRC资助的研究中，我们已经表明，食物线索激活了大脑中与奖励和动机有关的区域中的稀疏神经元集，称为“神经元集合”，例如前额皮质和伏隔核(例如Ziminski等人)。2017年；PMID：28213443；Brebner等人。2020年；PMID：3172294)。然而，对于EE如何通过调节食物线索暴露时这些脑区内的神经元活动模式来调节其行动，人们知之甚少。因此，本项目的目的是利用最先进的活体方法，如纤维光度学、光遗传学和组织学方法，揭示EE在这些大脑区域发挥作用的机制。英国有三分之二的人超重或肥胖，解决肥胖问题是英国政府的优先领域。此外，这些情况增加了患其他严重疾病的风险，如糖尿病和新冠肺炎的临床并发症，并给国民健康保险制度带来负担。因此，了解抑制食物寻找和食物消费的机制将具有重大的经济和社会影响。

In certain individuals, cue exposure elicits food cravings that contribute to overeating and obesity. Many studies have examined how the brain triggers reactions to cues and promote food seeking and consumption. However, an important and understudied aspect of cue reactivity research is how the brain harnesses anti-craving mechanisms to suppress food seeking and consumption. Interestingly, we have observed in mice that brief exposure to environmentally enriched (EE) housing, which provides cognitive and physical stimulation through toys and exercise, reduces both cue-triggered food seeking and food consumption. Thus, EE reduces the motivational impact of food cues and food. In our BBSRC-funded studies, we have shown that food cues activate sparse sets of neurons called 'neuronal ensembles' in brain areas implicated in reward and motivation, such as the prefrontal cortex and nucleus accumbens (e.g. Ziminski et al. 2017; PMID: 28213443; Brebner et al. 2020; PMID: 3172294). However, little is known about how EE mediates its actions by modulating the neuronal activity patterns within these brain areas upon food cue exposure. Thus, the aim of this project is to reveal the mechanisms behind EE's action in these brain areas using state-of-the-art in vivo methods, such as fibre photometry and optogenetics and histological methods. With 2 of 3 UK individuals overweight or obese, tackling obesity is a priority area for the UK government. Furthermore, these conditions increase the risks of developing other serious illnesses such as diabetes, and clinical complications from COVID-19 and burden the NHS. Hence, understanding the mechanisms that suppress food seeking and food consumption will have significant economic and societal impact.