Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA.
Nat Neurosci. 2014 Feb;17(2):262-8. doi: 10.1038/nn.3627. Epub 2014 Jan 19.
The reciprocal synapse between photoreceptors and horizontal cells underlies lateral inhibition and establishes the antagonistic center-surround receptive fields of retinal neurons to enhance visual contrast. Despite decades of study, the signal mediating the negative feedback from horizontal cells to cones has remained under debate because the small, invaginated synaptic cleft has precluded measurement. Using zebrafish retinas, we show that light elicits a change in synaptic proton concentration with the correct magnitude, kinetics and spatial dependence to account for lateral inhibition. Light, which hyperpolarizes horizontal cells, causes synaptic alkalinization, whereas activating an exogenously expressed ligand-gated Na(+) channel, which depolarizes horizontal cells, causes synaptic acidification. Whereas acidification was prevented by blocking a proton pump, re-alkalinization was prevented by blocking proton-permeant ion channels, suggesting that distinct mechanisms underlie proton efflux and influx. These findings reveal that protons mediate lateral inhibition in the retina, raising the possibility that protons are unrecognized retrograde messengers elsewhere in the nervous system.
光感受器和水平细胞之间的相互突触是横向抑制的基础，并建立了视网膜神经元的拮抗中心-环绕感受野，以增强视觉对比度。尽管经过了几十年的研究，但由于小的、内陷的突触裂隙使得测量变得困难，因此介导水平细胞向视锥细胞的负反馈的信号仍然存在争议。使用斑马鱼视网膜，我们发现光引发了突触质子浓度的变化，其幅度、动力学和空间依赖性都正确，可以解释横向抑制。光使水平细胞超极化，导致突触碱化，而激活外源性表达的配体门控 Na(+)通道，使水平细胞去极化，导致突触酸化。虽然通过阻断质子泵可以防止酸化，但通过阻断质子可渗透的离子通道可以防止再碱化，这表明质子外流和内流的机制不同。这些发现表明质子介导了视网膜中的横向抑制，这增加了质子在神经系统其他部位作为未被识别的逆行信使的可能性。
