Resilience against food cravings via environmental enrichment (EE): neuronal ensemble mechanisms

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1 in 4 people in the UK are now obese and recent NHS figures indicate ~£6.1 billion is spent on treatment of overweight and obesity-related ill-health. Obesity may result from excessive eating and increases the risk of debilitating diseases (e.g. cancer). Stimuli called 'cues' (e.g. the sights/smells of food, food advertisements) trigger us to crave, seek, and eat foods. Thus, we need to identify how we can increase our resilience against these effects of food cues to better manage eating-related behaviours. Although many studies have revealed how cues trigger cravings in the brain, little is known about how it produces 'anti-craving' effects.Interestingly, a brief experience of physical and cognitive stimulation (e.g. walking, playing Tetris) reduces cravings and the attractiveness of food cues. Similarly, in laboratory animals such stimulation via brief exposure to items such as exercise wheels and toys called 'environmental enrichment' (EE) powerfully reduces food seeking triggered by food cues. As such, EE is a useful approach to investigate increased resilience against reactions to cues and cravings. The prefrontal cortex is implicated in suppressing urges and regulating food cravings, which are impaired in obese patients. In animals, food cues mobilise or 'recruit' specific groups or 'ensembles' of neurons to suppress or promote food seeking in this brain area. Also, when food seeking levels change, ensembles change their 'electrical' properties. In turn, this controls the rapid 'activity' of neurons which interprets information about cues. These properties are regulated by ion channels, which are viewed as important therapeutic targets for various diseases. We recently found that brief EE exposure robustly reduced food seeking and ensemble recruitment in the prefrontal cortex triggered by food cues in hungry mice. But what is the precise identity of this dynamically regulated ensemble following EE? Our aim here is to reveal how EE suppresses food seeking triggered by food cues through two possible prefrontal cortex actions by: i) adjusting the recruitment, excitability, or rapid activity properties of an 'existing' food seeking ensemble; and/or ii) actively recruiting a 'new' ensemble during cue exposure with unique excitability or rapid activity properties. We will examine the properties of prefrontal cortex ensembles activated by food seeking before and after EE. Notably, since this deep brain area is difficult to image, we will take advantage of a glass 'microprism' to image how ensembles are recruited and rapidly activated. We will also selectively activate an ensemble and determine the causal link between ensemble activity and suppression of food seeking. Furthermore, we will use electrophysiology to characterise electrical state alterations of ensembles. We will reveal how specific groups of neurons with altered physiological properties reduce reactions to food cues. Such knowledge will provide the crucial building blocks to develop novel therapeutic strategies that engage anti-craving mechanisms to combat obesity.