Homeostatic circuits selectively gate food cue responses in insular cortex
- 14 June 2017
- journal article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 546 (7660), 611-616
- https://doi.org/10.1038/nature22375
Abstract
Physiological needs bias perception and attention to relevant sensory cues. This process is ‘hijacked’ by drug addiction, causing cue-induced cravings and relapse. Similarly, its dysregulation contributes to failed diets, obesity, and eating disorders. Neuroimaging studies in humans have implicated insular cortex in these phenomena. However, it remains unclear how ‘cognitive’ cortical representations of motivationally relevant cues are biased by subcortical circuits that drive specific motivational states. Here we develop a microprism-based cellular imaging approach to monitor visual cue responses in the insular cortex of behaving mice across hunger states. Insular cortex neurons demonstrate food-cue-biased responses that are abolished during satiety. Unexpectedly, while multiple satiety-related visceral signals converge in insular cortex, chemogenetic activation of hypothalamic ‘hunger neurons’ (expressing agouti-related peptide (AgRP)) bypasses these signals to restore hunger-like response patterns in insular cortex. Circuit mapping and pathway-specific manipulations uncover a pathway from AgRP neurons to insular cortex via the paraventricular thalamus and basolateral amygdala. These results reveal a neural basis for state-specific biased processing of motivationally relevant cues. A combination of microprism-based cellular imaging to monitor insular cortex visual cue responses in behaving mice across hunger states with circuit mapping and manipulations reveals a neural basis for state-specific biased processing of motivationally relevant cues. Physiological states can directly bias an animal's attention towards those cues in the environment that are most relevant to its immediate needs. However, our understanding of how the brain drives behaviours directed towards meeting those motivated needs is limited. Here Mark Andermann and colleagues reveal that, during a behavioural task, mice insular cortical neurons were strongly biased towards visual cues representing food when the animals were hungry, but these biases were not apparent following satiation. Insular neural responses to the cues were modulated by the activity levels of hypothalamic AgRP neurons, which drive feeding behaviour. Artificial activation of these neurons over-rode satiety signals and reinstated biased responses by insular neurons to food-related task cues. Neurons driving and responding to specific motivated states can influence and bias cognitive processing of salient cues.Keywords
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