Debertin Gábor, Kántor Orsolya, Kovács-Öller Tamás, Balogh Lajos, Szabó-Meleg Edina, Orbán József, Nyitrai Miklós, Völgyi Béla
Department of Experimental Zoology and Neurobiology, University of Pécs, Pécs, Hungary.
János Szentágothai Research Center, Pécs, Hungary.
J Neurochem. 2015 Aug;134(3):416-28. doi: 10.1111/jnc.13144. Epub 2015 Jun 3.
Dopaminergic neurons of the central nervous system are mainly found in nuclei of the midbrain and the hypothalamus that provide subcortical and cortical targets with a rich and divergent innervation. Disturbance of signaling through this system underlies a variety of deteriorating conditions such as Parkinson's disease and schizophrenia. Although retinal dopaminergic signaling is largely independent of the above circuitry, malfunction of the retinal dopaminergic system has been associated with anomalies in visual adaptation and a number of retinal disorders. Dopamine (DA) is released mainly in a paracrine manner by a population of tyrosine hydroxylase expressing (TH(+) ) amacrine cells (AC) of the mammalian retina; thus DA reaches virtually all retinal cell types by diffusion. Despite this paracrine release, however, the so called AII ACs have been considered as the main targets of DA signaling owing to a characteristic and robust ring-like TH(+) innervation to the soma/dendritic-stalk area of AII cells. This apparent selectivity of TH(+) innervation seems to contradict the divergent DAergic signaling scheme of other brain loci. In this study, however, we show evidence for intimate proximity between TH(+) rings and somata of neurochemically identified non-AII cells. We also show that this phenomenon is not species specific, as we observe it in popular mammalian animal models including the rabbit, the rat, and the mouse. Finally, our dataset suggests the existence of further, yet unidentified post-synaptic targets of TH(+) dendritic rings. Therefore, we hypothesize that TH(+) ring-like structures target the majority of ACs non-selectively and that such contacts are wide-spread among mammals. Therefore, this new view of inner retinal TH(+) innervation resembles the divergent DAergic innervation of other brain areas through the mesolimbic, mesocortical, and mesostriatal signaling streams. AII amacrine cells have been considered as the main targets of dopamine signaling in the mammalian retina owing to a characteristic ring-like innervation from dopaminergic (TH(+) ) amacrine cells (green) to somata of AII cells (red). In this study, we show the intimate proximity of TH(+) rings and somata of non-AII cells, including starburst-a amacrine cells (blue) and other unidentified amacrine cells (magenta). We find that this phenomenon is not species specific and it occurs in a number of popular mammalian animal models. We hypothesize that TH(+) ring-inputs target most amacrine cells non-selectively and thus it resembles the divergent dopaminergic innervation of other brain areas.
中枢神经系统中的多巴胺能神经元主要存在于中脑和下丘脑的核团中,这些核团为皮层下和皮层靶点提供丰富且分散的神经支配。通过该系统的信号传导紊乱是帕金森病和精神分裂症等多种恶化病症的基础。尽管视网膜多巴胺能信号传导在很大程度上独立于上述神经回路,但视网膜多巴胺能系统的功能障碍已与视觉适应异常和多种视网膜疾病相关联。多巴胺(DA)主要以旁分泌方式由哺乳动物视网膜中一群表达酪氨酸羟化酶(TH(+))的无长突细胞(AC)释放;因此,DA通过扩散几乎到达所有视网膜细胞类型。然而,尽管存在这种旁分泌释放,但由于对AII细胞的胞体/树突柄区域具有特征性且强烈的环状TH(+)神经支配,所谓的AII无长突细胞一直被认为是DA信号传导的主要靶点。TH(+)神经支配的这种明显选择性似乎与其他脑区的分散性多巴胺能信号传导模式相矛盾。然而,在本研究中,我们展示了TH(+)环与神经化学鉴定的非AII细胞的胞体紧密相邻的证据。我们还表明,这种现象不是物种特异性的,因为我们在包括兔子、大鼠和小鼠在内的常见哺乳动物动物模型中都观察到了这一现象。最后,我们的数据集表明存在尚未确定的TH(+)树突环的其他突触后靶点。因此,我们假设TH(+)环状结构非选择性地靶向大多数无长突细胞,并且这种接触在哺乳动物中广泛存在。因此,视网膜内层TH(+)神经支配的这种新观点类似于通过中脑边缘、中脑皮质和中脑纹状体信号传导通路对其他脑区的分散性多巴胺能神经支配。由于多巴胺能(TH(+))无长突细胞(绿色)对AII细胞(红色)的胞体具有特征性的环状神经支配,AII无长突细胞一直被认为是哺乳动物视网膜中多巴胺信号传导的主要靶点。在本研究中,我们展示了TH(+)环与非AII细胞的胞体紧密相邻,包括星爆 - a无长突细胞(蓝色)和其他未鉴定的无长突细胞(品红色)。我们发现这种现象不是物种特异性的,并且在一些常见的哺乳动物动物模型中都会发生。我们假设TH(+)环输入非选择性地靶向大多数无长突细胞,因此它类似于其他脑区的分散性多巴胺能神经支配。