Vroman Rozan, Kamermans Maarten
Retinal Signal Processing Lab, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands.
Department of Neurogenetics, University of Amsterdam, Academic Medical Centre, Meibergdreef 15, 1105 AZ, Amsterdam, Netherlands.
J Physiol. 2015 Jul 1;593(13):2927-40. doi: 10.1113/JP270158. Epub 2015 May 11.
In the retina, horizontal cells feed back negatively to cone photoreceptors. Glutamate released from cones can spill over to neighbouring cones. Here we show that cone glutamate release induced by negative feedback can also spill over to neighbouring cones. This glutamate activates the glutamate transporter-associated chloride current in these neighbouring cones, which leads to a change in their membrane potential and thus modulates their output. In this way, feedback-induced glutamate spillover enhances negative feedback from horizontal cells to cones, thus forming an additional feedback pathway. This effect will be particularly prominent in cones that are strongly hyperpolarized by light.
Inhibition in the outer retina functions via an unusual mechanism. When horizontal cells hyperpolarize the activation potential of the Ca(2+) current of cones shifts to more negative potentials. The underlying mechanism consists of an ephaptic component and a Panx1/ATP-mediated component. Here we identified a third feedback component, which remains active outside the operating range of the Ca(2+) current. We show that the glutamate transporters of cones can be activated by glutamate released from their neighbours. This pathway can be triggered by negative feedback from horizontal cells to cones, thus providing an additional feedback pathway. This additional pathway is mediated by a Cl(-) current, can be blocked by either removing the gradient of K(+) or by adding the glutamate transporter blocker TBOA, or low concentrations of Zn(2+) . These features point to a glutamate transporter-associated Cl(-) current. The pathway has a delay of 4.7 ± 1.7 ms. The effectiveness of this pathway in modulating the cone output depends on the equilibrium potential of Cl(-) (ECl ) and the membrane potential of the cone. Because estimates of ECl show that it is around the dark resting membrane potential of cones, the activation of the glutamate transporter-associated Cl(-) current will be most effective in changing the membrane potential during strong hyperpolarization of cones. This means that negative feedback would particularly be enhanced by this pathway when cones are hyperpolarized. Spatially, this pathway does not reach further than the direct neighbouring cones. The consequence is that this feedback pathway transmits information between cones of different spectral type.
在视网膜中，水平细胞对视锥光感受器进行负反馈。视锥释放的谷氨酸能扩散到相邻视锥。在此我们表明，由负反馈诱导的视锥谷氨酸释放也能扩散到相邻视锥。这种谷氨酸激活这些相邻视锥中与谷氨酸转运体相关的氯电流，导致其膜电位变化，从而调节其输出。通过这种方式，反馈诱导的谷氨酸扩散增强了水平细胞对视锥的负反馈，从而形成一条额外的反馈途径。这种效应在被光强烈超极化的视锥中尤为显著。
视网膜外层的抑制作用通过一种不同寻常的机制发挥。当水平细胞超极化时，视锥钙电流的激活电位会向更负的电位移动。其潜在机制包括电突触成分和Panx1/ATP介导的成分。在此我们发现了第三个反馈成分，它在钙电流的工作范围之外仍保持活性。我们表明，视锥的谷氨酸转运体可被其相邻视锥释放的谷氨酸激活。这条途径可由水平细胞对视锥的负反馈触发，从而提供一条额外的反馈途径。这条额外途径由氯电流介导，可通过消除钾离子梯度、添加谷氨酸转运体阻滞剂TBOA或低浓度的锌离子来阻断。这些特征指向一种与谷氨酸转运体相关的氯电流。该途径的延迟为4.7±1.7毫秒。这条途径调节视锥输出的有效性取决于氯的平衡电位（ECl）和视锥的膜电位。由于ECl的估计值表明它接近视锥的暗静息膜电位，因此与谷氨酸转运体相关的氯电流的激活在视锥强烈超极化期间改变膜电位时将最为有效。这意味着当视锥超极化时，这条途径会特别增强负反馈。在空间上，这条途径不会延伸到直接相邻视锥之外。结果是，这条反馈途径在不同光谱类型的视锥之间传递信息。
