A proposed hypothalamic-thalamic-striatal axis for the integration of energy balance, arousal, and food reward
A proposed hypothalamic-thalamic-striatal axis for the integration of energy balance, arousal, and food reward
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DOI：
10.1002/cne.20769
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发表时间：
2005-12-05
影响因子：
2.5
通讯作者：
Pratt, WE
中科院分区：
文献类型：
--
作者：
Kelley, AE;Baldo, BA;Pratt, WE
我们在此详细阐述了一种关于基底神经节功能的新理论，该理论解释了为什么即使在满足了直接生理能量需求的情况下，美味、高能量的食物仍能保持高激励价值。基底神经节的功能已经从并行电路中处理的地形隔离的角度进行了研究，主要关注运动控制和认知。然而，最近的研究结果表明，纹状体可以作为一个综合单元来调节动机状态。我们描述了纹状体脑啡肽系统的证据，它调节了偏好食物的享乐影响，经历了与食物摄入相关的当前动机状态的协调基因表达变化。纹状体脑啡肽基因表达也可通过纹状体内注入胆碱能毒蕈碱拮抗剂而下调，这一操作可极大地抑制食物摄入。为了解释这些发现，我们提出通过下丘脑中线丘脑纹状体轴的信号冲击纹状体的胆碱能中间神经元，这些神经元通过它们巨大的重叠轴突场作为一个网络来调节含有脑啡肽的纹状体输出神经元。该回路的一个关键中继是室旁丘脑核，它接收来自食欲素编码的下丘脑能量感知和行为状态调节神经元以及昼夜节律振荡器的收敛输入，并投射到纹状体复合体的胆碱能中间神经元。我们假设，这个系统的进化是为了协调进食和觉醒，并延长进食的中心动机状态，从而促进“暴饮暴食”，从而为潜在的未来食物短缺发展能量储备。
We elaborate herein a novel theory of basal ganglia function that accounts for why palatable, energy-dense foods retain high incentive value even when immediate physiological energy requirements have been met. Basal ganglia function has been studied from the perspective of topographical segregation of processing within parallel circuits, with primary focus on motor control and cognition. Recent findings suggest, however, that the striatum can act as an integrated unit to modulate motivational state. We describe evidence that the striatal enkephalin system, which regulates the hedonic impact of preferred foods, undergoes coordinated gene expression changes that track current motivational state with regard to food intake. Striatal enkephalin gene expression is also downregulated by an intrastriatal infusion of a cholinergic muscarinic antagonist, a manipulation that greatly suppresses food intake. To account for these findings, we propose that signaling through a hypothalamicmidline thalamic-striatal axis impinges on the cholinergic interneurons of the striatum, which via their large, overlapping axonal fields act as a network to modulate enkephalin-containing striatal output neurons. A key relay in this circuit is the paraventricular thalamic nucleus, which receives convergent input from orexin-coded hypothalamic energy-sensing and behavioral state-regulating neurons, as well as from circadian oscillators, and projects to cholinergic interneurons throughout the striatal complex. We hypothesize that this system evolved to coordinate feeding and arousal, and to prolong the feeding central motivational state beyond the fulfillment of acute energy needs, thereby promoting "overeating" and the consequent development of an energy reserve for potential future food shortages.