Human and Evolutionary Biology Section, Department of Biological Sciences, University of Southern California, Los Angeles, CA, 90089, USA.
Department of Foods and Nutrition, University of Georgia, Athens, GA, 30606, USA.
Nat Commun. 2019 Oct 29;10(1):4923. doi: 10.1038/s41467-019-12895-y.
Behavioral impulsivity is common in various psychiatric and metabolic disorders. Here we identify a hypothalamus to telencephalon neural pathway for regulating impulsivity involving communication from melanin-concentrating hormone (MCH)-expressing lateral hypothalamic neurons to the ventral hippocampus subregion (vHP). Results show that both site-specific upregulation (pharmacological or chemogenetic) and chronic downregulation (RNA interference) of MCH communication to the vHP increases impulsive responding in rats, indicating that perturbing this system in either direction elevates impulsivity. Furthermore, these effects are not secondary to either impaired timing accuracy, altered activity, or increased food motivation, consistent with a specific role for vHP MCH signaling in the regulation of impulse control. Results from additional functional connectivity and neural pathway tracing analyses implicate the nucleus accumbens as a putative downstream target of vHP MCH1 receptor-expressing neurons. Collectively, these data reveal a specific neural circuit that regulates impulsivity and provide evidence of a novel function for MCH on behavior.
行为冲动在各种精神和代谢紊乱中很常见。在这里，我们确定了一个调节冲动的下丘脑到端脑神经通路，涉及到表达黑色素聚集激素（MCH）的外侧下丘脑神经元向腹侧海马亚区（vHP）的通讯。结果表明，MCH 向 vHP 的特定部位上调（药理学或化学遗传学）和慢性下调（RNA 干扰）都增加了大鼠的冲动反应，表明该系统的任何方向的干扰都会增加冲动性。此外，这些影响并不是由于时间准确性受损、活动改变或食物动机增加所致，这与 vHP MCH 信号在冲动控制调节中的特定作用一致。来自其他功能连接和神经通路追踪分析的结果表明，伏隔核是 vHP MCH1 受体表达神经元的一个潜在下游靶点。总的来说，这些数据揭示了一个调节冲动性的特定神经回路，并为 MCH 在行为中的新功能提供了证据。
