Gallardo Christian M, Darvas Martin, Oviatt Mia, Chang Chris H, Michalik Mateusz, Huddy Timothy F, Meyer Emily E, Shuster Scott A, Aguayo Antonio, Hill Elizabeth M, Kiani Karun, Ikpeazu Jonathan, Martinez Johan S, Purpura Mari, Smit Andrea N, Patton Danica F, Mistlberger Ralph E, Palmiter Richard D, Steele Andrew D
Division of Biology, California Institute of Technology, Pasadena, United States.
Department of Pathology, University of Washington, Seattle, United States.
Elife. 2014 Sep 12;3:e03781. doi: 10.7554/eLife.03781.
Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive. In this study, we show that mice lacking the dopamine D1 receptor (D1R KO mice) manifest greatly reduced FAA, whereas mice lacking the dopamine D2 receptor have normal FAA. To determine where dopamine exerts its effect, we limited expression of dopamine signaling to the dorsal striatum of dopamine-deficient mice; these mice developed FAA. Within the dorsal striatum, the daily rhythm of clock gene period2 expression was markedly suppressed in D1R KO mice. Pharmacological activation of D1R at the same time daily was sufficient to establish anticipatory activity in wild-type mice. These results demonstrate that dopamine signaling to D1R-expressing neurons in the dorsal striatum plays an important role in manifestation of FAA, possibly by synchronizing circadian oscillators that modulate motivational processes and behavioral output.
食物预期活动(FAA)的每日节律是独立于视交叉上核调节的,视交叉上核介导节律与光的同步,但建立FAA的神经回路仍然难以捉摸。在本研究中,我们发现缺乏多巴胺D1受体的小鼠(D1R基因敲除小鼠)表现出FAA大幅降低,而缺乏多巴胺D2受体的小鼠FAA正常。为了确定多巴胺发挥作用的位置,我们将多巴胺信号的表达限制在多巴胺缺乏小鼠的背侧纹状体;这些小鼠出现了FAA。在背侧纹状体内,D1R基因敲除小鼠中生物钟基因period2表达的每日节律明显受到抑制。每天同一时间对D1R进行药理学激活足以在野生型小鼠中建立预期活动。这些结果表明,向背侧纹状体中表达D1R的神经元传递多巴胺信号在FAA的表现中起重要作用,可能是通过同步调节动机过程和行为输出的昼夜节律振荡器来实现的。