AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors
AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors
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DOI：
10.1038/nn.3147
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发表时间：
2012-08-01
影响因子：
25
通讯作者：
Horvath, Tamas L.
中科院分区：
文献类型：
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作者：
Dietrich, Marcelo O.;Bober, Jeremy;Horvath, Tamas L.
目前尚不清楚与进食无关的行为是否受到饥饿下丘脑调节器的影响。我们发现，无论是Sirt1敲低AgRP表达的神经元或这些神经元的出生后早期消融Agouti相关蛋白（AgRP）电路的损害增加了探索行为和可卡因的反应增强。在AgRP电路受损的小鼠，腹侧被盖多巴胺神经元表现出增强的尖峰时间依赖性的长时程增强，改变幅度的微型突触后电流和基底前脑多巴胺升高。因此，AgRP神经元决定了奖励回路和相关行为的设定点。
It is not known whether behaviors unrelated to feeding are affected by hypothalamic regulators of hunger. We found that impairment of Agouti-related protein (AgRP) circuitry by either Sirt1 knockdown in AgRP-expressing neurons or early postnatal ablation of these neurons increased exploratory behavior and enhanced responses to cocaine. In AgRP circuit-impaired mice, ventral tegmental dopamine neurons exhibited enhanced spike timing-dependent long-term potentiation, altered amplitude of miniature postsynaptic currents and elevated dopamine in basal forebrain. Thus, AgRP neurons determine the set point of the reward circuitry and associated behaviors.