多巴胺D1受体在小鼠大脑皮层的空间分布研究
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摘要
目的:利用多巴胺受体1(D1Rs)荧光转基因小鼠系统探讨D1Rs在小鼠大脑皮层的空间分布特征和相对表达模式。方法:使用成年Drd1-tdTomato转基因小鼠,制备冠状全脑切片,采用DAPI衬染细胞核,在共聚焦显微镜下观察D1Rs的分布,使用Imaris软件荧光阈值点自动计数算法实现细胞计数。结果:D1Rs在大多数大脑皮层区域内都有表达,但总体比例较低,这些区域包括眶皮层、岛叶皮层、扣带皮层、视皮层、听觉皮层、运动皮层、躯体感觉皮层、外嗅皮层和梨状皮层等。同时我们发现D1Rs在大脑皮层中主要集中在浅层(1/2层)和深层(5/6层)。结论:不同大脑皮层区域D1Rs分布模式不同。
Objective: Using dopamine receptors D1(D1Rs) transgenic mice to explore the distribution and relative expression patterns of D1Rs in different cortical regions systematically. Methods: Adult Drdl-tdTomato transgenic mice were used for preparing coronal brain slices containing the whole brain,DAPI was used to stain nuclei. Observations were carried out under the confocal microscope. And the expression patterns of D1Rs were determined by counting the number of cells achieved by automatic spots algorithm based on the fluorescent threshold using the Imaris software.Results: D1Rs expressed in most cerebral cortex regions but totally in a relatively low proportion,such as orbital cortex,insular cortex,cingulate cortex,visual cortex,auditory cortex,motor cortex,somatosensory cortex,piriform cortex and ectorhinal cortex. And we found that the expression of D1Rs in cerebral cortex was mostly in the superficial(layers1/2) and deep layers(layers 5/6). Conclusion: There is a variable distribution pattern of D1Rs in cerebral cortex regions.
Objective: Using dopamine receptors D1(D1Rs) transgenic mice to explore the distribution and relative expression patterns of D1Rs in different cortical regions systematically. Methods: Adult Drdl-tdTomato transgenic mice were used for preparing coronal brain slices containing the whole brain,DAPI was used to stain nuclei. Observations were carried out under the confocal microscope. And the expression patterns of D1Rs were determined by counting the number of cells achieved by automatic spots algorithm based on the fluorescent threshold using the Imaris software.Results: D1Rs expressed in most cerebral cortex regions but totally in a relatively low proportion,such as orbital cortex,insular cortex,cingulate cortex,visual cortex,auditory cortex,motor cortex,somatosensory cortex,piriform cortex and ectorhinal cortex. And we found that the expression of D1Rs in cerebral cortex was mostly in the superficial(layers1/2) and deep layers(layers 5/6). Conclusion: There is a variable distribution pattern of D1Rs in cerebral cortex regions.
引文
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[2]Puig MV,Antzoulatos EG,Miller EK,et al.Prefrontal dopamine in associative learning and memory[J].Neuroscience,2014,282:217-229.DOI:10.1016/j.neuroscience.2014.09.026.
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[5]Missale C,Nash SR,Robinson SW,et al.Dopamine receptors:from structure to function[J].Physiol Rev,1998,78(1):189-225.DOI:10.1152/physrev.1998.78.1.189.
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[8]Castner SA,Williams GV,Goldman-Rakic PS,et al.Reversal of antipsychotic-induced working memory deficits by short-term dopamine D1 receptor stimulation[J].Science,2000,287(5460):2020-2022.DOI:10.1126/science.287.5460.2020.
[9]Karabacak Y,Sase S,Aher YD,et al.The effect of modafinil on the rat dopamine transporter and dopamine receptors D1-D3 paralleling cognitive enhancement in the radial arm maze[J].Front Behav Neurosci,2015,9:215.DOI:10.3389/fnbeh.2015.00215.
[10]Hernadi L,Vehovszky A,Serfozo Z.Immunological and pharmacological identification of the dopamine D1 receptor in the CNS of the pond snail,Lymnaea stagnalis[J].Acta Biol Hung,2012,63Suppl 2:151-159.DOI:10.1556/ABiol.63.2012.Suppl.2.20.
[11]Pantazopoulos H,Stone D,Walsh J,et al.Differences in the cellular distribution of D1 receptor m RNA in the hippocampus of bipolars and schizophrenics[J].Synapse,2004,54(3):147-155.DOI:10.1002/syn.20076.
[12]Sesack SR,Aoki C,Pickel VM,et al.Ultrastructural localization of D2 receptor-like immunoreactivity in midbrain dopamine neurons and their striatal targets[J].J Neurosci,1994,14(1):88-106.DOI:10.1523/JNEUROSCI.14-01-00088.1994.
[13]Gong S,Zheng C,Doughty ML,et al.A gene expression atlas of the central nervous system based on bacterial artificial chromosomes[J].Nature,2003,425(6961):917-925.DOI:10.1038/nature02033.
[14]Cao J,Dorris DM,Meitzen J.Electrophysiological properties of medium spiny neurons in the nucleus accumbens core of prepubertal male and female Drd1a-tdTomato line 6 BAC transgenic mice[J].J Neurophysiol,2018,120(4):1712-1727.DOI:10.1152/jn.00257.2018.
[15]Franklin K,Paxinos G.The mouse brain in stereotaxic coordinates[M].2nd edition,Amsterdam,the Netherlands:Academic Press Elsevier,2001.
[16]Koyama Y,Kondo M,Shimada S.Building a 5-HT3A receptor expression map in the mouse brain[J].Sci Rep,2017,7(1):42884.DOI:10.1038/srep42884.
[17]Xu L,Zhang XH.Distribution of D1 and D2-dopamine receptors in calcium-binding-protein expressing interneurons in rat anterior cingulate cortex[J].Sheng Li Xue Bao,2015,67(2):163-172.DOI:10.13294/j.aps.2015.0019.
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[19]Kerr KM,Agster KL,Furtak SC,et al.Functional neuroanatomy of the parahippocampal region:the lateral and medial entorhinal areas[J].Hippocampus,2007,17(9):697-708.DOI:10.1002/hipo.20315.
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[22]Land BB,Narayanan NS,Liu RJ,et al.Medial prefrontal D1 dopamine neurons control food intake[J].Nat Neurosci,2014,17(2):248-253.DOI:10.1038/nn.3625.
[23]Rinaldi A,Mandillo S,Oliverio A,et al.D1 and D2 receptor antagonist injections in the prefrontal cortex selectively impair spatial learning in mice[J].Neuropsychopharmacology,2007,32(2):309-319.DOI:10.1038/sj.npp.1301176.
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