Type 1 dopamine receptor (D1R)-independent circadian food anticipatory activity in mice.
Type 1 dopamine receptor (D1R)-independent circadian food anticipatory activity in mice.
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DOI：
10.1371/journal.pone.0242897
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Steele AD
中科院分区：
文献类型：
--
作者：
Assali DR;Sidikpramana M;Villa AP;Falkenstein J;Steele AD
昼夜节律受光和非光刺激（如摄食）的影响。在预定进餐时间之前的活动，即食物预期活动（FAA），是在预定时间内以有限的量喂养的啮齿动物中引起的。FAA被认为是一个身份不明的食物夹带振荡器的输出。先前的研究，利用基因缺失和受体药理学，暗示多巴胺型受体1 （D1R）信号在背纹状体是必需的FAA小鼠。为了进一步了解D1R在促进FAA中的作用，我们利用Cre-lox系统创建细胞类型特异性D1R缺失，使用Vgat-ires-Cre系有条件地删除GABA神经元中的D1R。该条件缺失突变体减弱了FAA，但数量高于先前使用D1R （D1R KODrago）组成性敲除的结果。这一结果促使我们重新测试原始D1R KODrago线，其表达较少的FAA比控制，但只有适度。为了确定遗传漂变是否减少了D1R缺失对FAA的影响，我们从冷冻保存的样本中重新建立了D1R KODrago敲除系。与对照组相比，重建的D1R KODrago-cryo的FAA明显受损，但在4周的定时喂养期间，进食前的活动仍然增加。最后，我们测试了敲除小鼠项目创建的D1R的不同缺失等位基因。D1R KOKOMP小鼠在获得FAA方面有明显的损伤，但在4周的定时喂养后，最终达到了与对照组相似的餐前活性水平。综上所述，我们的研究结果表明D1R信号促进FAA，但其他多巴胺受体可能有助于FAA，因为缺乏D1受体的小鼠仍然保留一些FAA。
Circadian rhythms are entrained by light and influenced by non-photic stimuli, such as feeding. The activity preceding scheduled mealtimes, food anticipatory activity (FAA), is elicited in rodents fed a limited amount at scheduled times. FAA is thought to be the output of an unidentified food entrained oscillator. Previous studies, using gene deletion and receptor pharmacology, implicated dopamine type receptor 1 (D1R) signaling in the dorsal striatum as necessary for FAA in mice. To further understand the role of D1R in promoting FAA, we utilized the Cre-lox system to create cell type-specific deletions of D1R, conditionally deleting D1R in GABA neurons using Vgat-ires-Cre line. This conditional deletion mutant had attenuated FAA, but the amount was higher than expected based on prior results using a constitutive knockout of D1R, D1R KODrago. This result prompted us to re-test the original D1R KODrago line, which expressed less FAA than controls, but only moderately so. To determine if genetic drift had diminished the effect of D1R deletion on FAA, we re-established the D1R KODrago knockout line from cryopreserved samples. The reestablished D1R KODrago-cryo had a clear impairment of FAA compared to controls, but still developed increased activity preceding mealtime across the 4 weeks of timed feeding. Finally, we tested a different deletion allele of D1R created by the Knockout Mouse Project. This line of D1R KOKOMP mice had a significant impairment in the acquisition of FAA, but eventually reached similar levels of premeal activity compared to controls after 4 weeks of timed feeding. Taken together, our results suggest that D1R signaling promotes FAA, but other dopamine receptors likely contribute to FAA given that mice lacking the D1 receptor still retain some FAA.
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