An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger.
An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger.
复制标题
刺激性室室核向AGRP神经元电路，驱动饥饿。
作者：
饥饿是一种对生存至关重要的硬连线激励状态。下丘脑底部弓状核（ARC）中表达Agouti相关肽（AgRP）的神经元对其控制至关重要。它们被热量缺乏激活，当自然或人工刺激时，它们会强烈地引起强烈的饥饿感和随后的食物摄入。与它们在调节食欲中的强制性作用一致，AgRP神经元的遗传消融或药物遗传学抑制减少了摄食。AgRP神经元的兴奋性输入是热量缺乏诱导激活的关键，并且以其显著程度的热量状态依赖性突触可塑性而闻名。尽管兴奋性输入的重要作用，其来源一直是未知的。在这里，通过使用Cre重组酶激活的细胞特异性神经元映射技术，我们发现了强烈的兴奋性驱动，出乎意料地，从下丘脑室旁核，特别是从表达促甲状腺激素释放激素（TRH）和腺苷酸环化酶激活多肽（PACAP）的神经元亚群发出。药物遗传刺激这些传入神经元在饱足小鼠显着激活AgRP神经元，并诱导激烈的喂养。相反，在热量不足引起饥饿的小鼠中，急性抑制会减少进食。这些能够触发饥饿感的传入神经元的发现推进了对这种强烈动机状态是如何调节的理解。
Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to its control. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake. Consistent with their obligatory role in regulating appetite, genetic ablation or pharmacogenetic inhibition of AgRP neurons decreases feeding. Excitatory input to AgRP neurons is key in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric state-dependent synaptic plasticity. Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing Thyrotropin-releasing hormone (TRH) and Pituitary adenylate cyclase-activating polypeptide (PACAP). Pharmaco-genetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated.
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