The TRPM1 Channel Is Required for Development of the Rod ON Bipolar Cell-AII Amacrine Cell Pathway in the Retinal Circuit
The TRPM1 Channel Is Required for Development of the Rod ON Bipolar Cell-AII Amacrine Cell Pathway in the Retinal Circuit
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DOI：
10.1523/jneurosci.0824-17.2017
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发表时间：
2017-10-11
影响因子：
5.3
通讯作者：
Furukawa, Takahisa
中科院分区：
文献类型：
--
作者：
Kozuka, Takashi;Chaya, Taro;Furukawa, Takahisa
神经传递在中枢神经系统的神经回路形成中起着至关重要的作用。虽然神经传递是视网膜回路发育的关键调节因子，但个体突触传递的作用尚未完全了解。在目前的研究中，我们研究了从光感受器细胞到ON双极细胞的神经传递在发育中的作用，使用了两性突变小鼠系，这种传递被取消了。我们发现，ON双极阳离子通道TRPM1的缺失导致杆状双极末端的异常收缩，以及它们与无突细胞的突触连接数量减少。相反，这些组织学改变并不是由于ON双极性谷氨酸受体mGluR6或光受体谷氨酸转运体VGluT1的缺失而导致的总谷氨酸传递中断引起的。此外，TRPM1缺失导致AII无突细胞的总树突长度、分支数量和细胞体大小减少。激活的Go α，已知关闭TRPM1通道，与TRPM1相互作用并诱导杆双极终端的收缩。此外，channel rhodopin -2的过表达部分挽救了TRPM1（-/-）视网膜中杆状双极细胞的发育，而组成封闭形式的TRPM1的挽救作用低于天然形式的TRPM1。我们的研究结果表明，TRPM1通道的打开对于杆双极通路的建立至关重要。
Neurotransmission plays an essential role in neural circuit formation in the central nervous system (CNS). Although neurotransmission has been recently clarified as a key modulator of retinal circuit development, the roles of individual synaptic transmissions are not yet fully understood. In the current study, we investigated the role of neurotransmission from photoreceptor cells to ON bipolar cells in development using mutant mouse lines of both sexes in which this transmission is abrogated. We found that deletion of the ON bipolar cation channel TRPM1 results in the abnormal contraction of rod bipolar terminals and a decreased number of their synaptic connections with amacrine cells. In contrast, these histological alterations were not caused by a disruption of total glutamate transmission due to loss of the ON bipolar glutamate receptor mGluR6 or the photoreceptor glutamate transporter VGluT1. In addition, TRPM1 deficiency led to the reduction of total dendritic length, branch numbers, and cell body size in AII amacrine cells. Activated Go alpha, known to close the TRPM1 channel, interacted with TRPM1 and induced the contraction of rod bipolar terminals. Furthermore, overexpression of Channelrhodopsin-2 partially rescued rod bipolar cell development in theTRPM1(-/-) retina, whereas the rescue effect by a constitutively closed form of TRPM1 was lower than that by the native form. Our results suggest that TRPM1 channel opening is essential for rod bipolar pathway establishment in development.