Gamma oscillations organize top-down signalling to hypothalamus and enable food seeking
Gamma oscillations organize top-down signalling to hypothalamus and enable food seeking
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DOI：
10.1038/nature21066
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发表时间：
2017-02-09
期刊：
影响因子：
64.8
通讯作者：
Korotkova, Tatiana
中科院分区：
文献类型：
--
作者：
Carus-Cadavieco, Marta;Gorbati, Maria;Korotkova, Tatiana
人类和动物都在环境中寻求主要的奖励，即使这种奖励不符合当前的生理需求。这方面的一个例子是觅食行为和代谢需求之间的分离，这是一种众所周知的难以治疗的饮食失调症状。进食依赖于下丘脑中不同的细胞群（1-4），其活性也会随着进食开始的预期而变化（5-7）。下丘脑从外侧隔接受强烈的下行输入，而外侧隔又与皮层网络相连，但与进食相关的行为的认知调节尚未被理解。皮层认知处理（9，10）涉及伽马振荡（11-15），它支持记忆（16，17），注意力（18），认知灵活性（19）和感官反应（20）。这些功能通过未知的神经机制对摄食行为起着至关重要的作用。在这里，我们表明，协调伽马（30-90赫兹）振荡在外侧下丘脑和上游脑区组织小鼠的食物寻找行为。从生长抑素阳性的外侧隔细胞到外侧下丘脑的γ节律性输入唤起食物接近而不影响食物摄入。来自外侧隔的抑制性输入使外侧下丘脑神经元能够根据它们的进食相关活动单独发出信号，使它们在伽马振荡的不同阶段发射。上游，内侧前额叶皮质的预测提供伽马节律的输入到外侧隔，这些输入是因果关系与提高性能的食物奖励学习任务。总的来说，我们的工作确定了一个自上而下的途径，使用伽马同步来指导皮层下网络的活动，并通过下丘脑功能细胞群的动态重组来调节摄食行为。
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.