期刊
NATURE
卷 542, 期 7640, 页码 232-236出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nature21066
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资金
- Human Frontier Science Program (HFSP) [RGY0076/2012]
- Deutsche Forschungsgemeinschaft (DFG) [Exc 257 NeuroCure, SPP1665]
- NIH (the Collaborative Research in Computational Neuroscience, CRCNS) [1R01 NS067199]
- German-Israeli Foundation for Scientific Research and Development [GIF: I-1326-421.13/2015]
- Medical Research Council [1363890] Funding Source: researchfish
Both humans and animals seek primary rewards in the environment, even when such rewards do not correspond to current physiological needs. An example of this is a dissociation between food-seeking behaviour and metabolic needs, a notoriously difficult-to treat symptom of eating disorders. Feeding relies on distinct cell groups in the hypothalamus(1-4), the activity of which also changes in anticipation of feeding onset(5-7). The hypothalamus receives strong descending inputs from the lateral septum, which is connected, in turn, with cortical networks', but cognitive regulation of feeding-related behaviours is not yet understood. Cortical cognitive processing(9,10) involves gamma oscillations(11-15), which support memory(16,17), attention(18), cognitive flexibility(19) and sensory responses(20). These functions contribute crucially to feeding behaviour by unknown neural mechanisms. Here we show that coordinated gamma (30-90 Hz) oscillations in the lateral hypothalamus and upstream brain regions organize food seeking behaviour in mice. Gamma-rhythmic input to the lateral hypothalamus from somatostatin-positive lateral septum cells evokes food approach without affecting food intake. Inhibitory inputs from the lateral septum enable separate signalling by lateral hypothalamus neurons according to their feeding-related activity, making them fire at distinct phases of the gamma oscillation. Upstream, medial prefrontal cortical projections provide gamma rhythmic inputs to the lateral septum; these inputs are causally associated with improved performance in a food-rewarded learning task. Overall, our work identifies a top-down pathway that uses gamma synchronization to guide the activity of subcortical networks and to regulate feeding behaviour by dynamic reorganization of functional cell groups in the hypothalamus.
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