期刊
NATURE
卷 546, 期 7660, 页码 611-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature22375
关键词
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资金
- Center for Neuroanatomy with Neurotropic Viruses [P40RR018604]
- European Molecular Biology Organization postdoctoral fellowship
- Edmond and Lily Safra Center for Brain Sciences postdoctoral award
- Davis Family Foundation postdoctoral fellowship
- National Science Foundation Graduate Research Fellowship Program
- Sackler Scholars Program
- National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) NRSA [F31 DK105678, F32 DK103387]
- NIH New Innovator Award [DP2 DK105570, R01 DK109930]
- Klarman Family Foundation
- McKnight Scholar Award
- Pew Scholar Award
- Smith Family Foundation
- NIH [R01 DK075632, R01 DK096010, R01 DK089044, R01 DK111401, P30 DK046200, P30 DK057521]
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-cuebiased 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 pathwayspecific 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.
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