Aberrant gating of photic input to the suprachiasmatic circadian pacemaker of mice lacking the VPAC2 receptor
Aberrant gating of photic input to the suprachiasmatic circadian pacemaker of mice lacking the VPAC2 receptor
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DOI：
10.1523/jneurosci.5345-03.2004
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发表时间：
2004-04-07
影响因子：
5.3
通讯作者：
Piggins, HD
中科院分区：
文献类型：
--
作者：
Hughes, AT;Fahey, B;Piggins, HD
VIP通过VPAC（2）受体发挥作用，是下丘脑视交叉上核（SCN）昼夜节律起搏器维持和重置的关键信号通路;在缺乏VPAC（2）受体（Vipr 2（-/-））的小鼠中，SCN时钟基因表达和跑轮行为的昼夜节律被消除。在这里，使用pERK（磷酸化细胞外信号调节激酶1/2）和c-FOS的免疫组织化学检测，我们测试了是否门控的光输入到SCN是维持在这些明显的vipr 2（-/-）小鼠。在光照/黑暗和恒定黑暗条件下，野生型小鼠SCN中pERK和c-FOS的自发表达在主观白天显著高于主观夜晚;在Vipr 2（-/-）小鼠SCN中未检测到pERK和c-FOS的昼夜或昼夜变化。在恒定的黑暗中，在主观夜间而不是主观白天给予的光脉冲显著增加了野生型SCN中pERK和c-FOS的表达。相比之下，在主观白天和主观夜晚期间给予的光脉冲强烈地增加了Vipr 2（-/-）小鼠SCN中pERK和c-FOS的表达。虽然光刺激激活Vipr 2（-/-）小鼠SCN内的细胞内通路，但它们不参与核心时钟机制。光门控的缺乏，以及昼夜输出中普遍缺乏明显的节律，强烈表明SCN昼夜节律起搏器在Vipr 2（-/-）小鼠中完全功能失调。
VIP acting via the VPAC(2) receptor is implicated as a key signaling pathway in the maintenance and resetting of the hypothalamic suprachiasmatic nuclei (SCN) circadian pacemaker; circadian rhythms in SCN clock gene expression and wheel-running behavior are abolished in mice lacking the VPAC(2) receptor (Vipr2(-/-)). Here, using immunohistochemical detection of pERK (phosphorylated extracellular signal-regulated kinases 1/2) and c-FOS, we tested whether the gating of photic input to the SCN is maintained in these apparently arrhythmic Vipr2(-/-) mice. Under light/dark and constant darkness, spontaneous expression of pERK and c-FOS in the wild-type mouse SCN was significantly elevated during subjective day compared with subjective night; no diurnal or circadian variation in pERK or c-FOS was detected in the SCN of Vipr2(-/-) mice. In constant darkness, light pulses given during the subjective night but not the subjective day significantly increased expression of pERK and c-FOS in the wild-type SCN. In contrast, light pulses given during both subjective day and subjective night robustly increased expression of pERK and c-FOS in the Vipr2(-/-) mouse SCN. Although photic stimuli activate intracellular pathways within the SCN of Vipr2(-/-) mice, they do not engage the core clock mechanisms. The absence of photic gating, together with the general lack of overt rhythms in circadian output, strongly suggests that the SCN circadian pacemaker is completely dysfunctional in the Vipr2(-/-) mouse.