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Homeostatic circuits selectively gate food cue responses in insular cortex

Yoav Livneh, Rohan N. Ramesh, Christian R. Burgess, Kirsten M. Levandowski, Joseph C. Madara, Henning Fenselau, Glenn J. Goldey, Veronica E. Diaz, Nick Jikomes, Jon M. Resch, Bradford B. Lowell () and Mark L. Andermann ()
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Yoav Livneh: Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School
Rohan N. Ramesh: Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School
Christian R. Burgess: Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School
Kirsten M. Levandowski: Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School
Joseph C. Madara: Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School
Henning Fenselau: Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School
Glenn J. Goldey: Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School
Veronica E. Diaz: Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School
Nick Jikomes: Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School
Jon M. Resch: Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School
Bradford B. Lowell: Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School
Mark L. Andermann: Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School

Nature, 2017, vol. 546, issue 7660, 611-616

Abstract: 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.

Date: 2017
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DOI: 10.1038/nature22375

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