Goto Akihiro, Nakahara Ichiro, Yamaguchi Takashi, Kamioka Yuji, Sumiyama Kenta, Matsuda Michiyuki, Nakanishi Shigetada, Funabiki Kazuo
Department of Systems Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan; Laboratory of Bioimaging and Cell Signaling and Laboratory for Memory Mechanisms, Brain Science Institute, RIKEN, Saitama 351-0198, Japan; and.
Department of Systems Biology, Osaka Bioscience Institute, Osaka 565-0874, Japan; Laboratory of Molecular Cell Biology and Development, Graduate School of Biostudies, and.
Proc Natl Acad Sci U S A. 2015 May 26;112(21):6718-23. doi: 10.1073/pnas.1507121112. Epub 2015 May 11.
The selection of reward-seeking and aversive behaviors is controlled by two distinct D1 and D2 receptor-expressing striatal medium spiny neurons, namely the direct pathway MSNs (dMSNs) and the indirect pathway MSNs (iMSNs), but the dynamic modulation of signaling cascades of dMSNs and iMSNs in behaving animals remains largely elusive. We developed an in vivo methodology to monitor Förster resonance energy transfer (FRET) of the activities of PKA and ERK in either dMSNs or iMSNs by microendoscopy in freely moving mice. PKA and ERK were coordinately but oppositely regulated between dMSNs and iMSNs by rewarding cocaine administration and aversive electric shocks. Notably, the activities of PKA and ERK rapidly shifted when male mice became active or indifferent toward female mice during mating behavior. Importantly, manipulation of PKA cascades by the Designer Receptor recapitulated active and indifferent mating behaviors, indicating a causal linkage of a dynamic activity shift of PKA and ERK between dMSNs and iMSNs in action selection.
寻求奖励和厌恶行为的选择由两种不同的表达D1和D2受体的纹状体中等棘状神经元控制，即直接通路中型多棘神经元（dMSNs）和间接通路中型多棘神经元（iMSNs），但在行为动物中dMSNs和iMSNs信号级联的动态调节在很大程度上仍不清楚。我们开发了一种体内方法，通过在自由活动的小鼠中进行显微内窥镜检查来监测dMSNs或iMSNs中PKA和ERK活性的荧光共振能量转移（FRET）。通过给予可卡因奖励和厌恶电击，PKA和ERK在dMSNs和iMSNs之间受到协同但相反的调节。值得注意的是，在交配行为中，当雄性小鼠对雌性小鼠变得活跃或无动于衷时，PKA和ERK的活性会迅速转变。重要的是，通过设计受体对PKA级联进行操纵重现了活跃和无动于衷的交配行为，表明在行动选择中，dMSNs和iMSNs之间PKA和ERK的动态活性转变存在因果联系。
