Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT, USA.
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, USA.
J Physiol. 2021 Nov;599(22):5047-5060. doi: 10.1113/JP281717. Epub 2021 Aug 17.
M1 intrinsically photosensitive retinal ganglion cells (ipRGCs) are known to encode absolute light intensity (irradiance) for non-image-forming visual functions (subconscious vision), such as circadian photoentrainment and the pupillary light reflex. It remains unclear how M1 cells respond to relative light intensity (contrast) and patterned visual signals. The present study identified a special form of contrast sensitivity (suppressed-by-contrast) in M1 cells, suggesting a role of patterned visual signals in regulating non-image-forming vision and a potential role of M1 ipRGCs in encoding image-forming visual cues. The study also uncovered a synaptic mechanism and a retinal circuit mediated by vesicular glutamate transporter 3 (vGluT3) amacrine cells that underlie the suppressed-by-contrast response of M1 cells. M1 ipRGC subtypes (M1a and M1b) were revealed that are distinguishable based on synaptic connectivity with vGluT3 amacrine cells, receptive field properties, intrinsic photo sensitivity and membrane excitability, and morphological features, suggesting a division of visual tasks among discrete M1 subpopulations.
The M1 type ipRGC (intrinsically photosensitive retinal ganglion cell) is known to encode ambient light signals for non-image-forming visual functions such as circadian photo-entrainment and the pupillary light reflex. Here, we report that a subpopulation of M1 cells (M1a) in the mouse retina possess the suppressed-by-contrast (sbc) trigger feature that is a receptive field property previously found only in ganglion cells mediating image-forming vision. Using optogenetics and the dual patch clamp technique, we found that vesicular glutamate transporter 3 (vGluT3) (vGluT3) amacrine cells make glycinergic, but not glutamatergic, synapses specifically onto M1a cells. The spatiotemporal and pharmacological properties of visually evoked responses of M1a cells closely matched the receptive field characteristics of vGluT3 cells, suggesting a major role of the vGluT3 amacrine cell input in shaping the sbc trigger feature of M1a cells. We found that the other subpopulation of M1 cells (M1b), which did not receive a direct vGluT3 cell input, lacked the sbc trigger feature, being distinctively different from M1a cells in intrinsic photo responses, membrane excitability, receptive-field characteristics and morphological features. Together, the results reveal a retinal circuit that uses the sbc trigger feature to regulate irradiance coding and potentially send image-forming cues to non-image-forming visual centres in the brain.
已知 M1 型光感受器神经节细胞（ipRGCs）可编码非成像视觉功能（潜意识视觉）的绝对光强度（辐照度），例如昼夜节律光适应和瞳孔光反射。目前尚不清楚 M1 细胞如何对相对光强度（对比度）和图案视觉信号做出反应。本研究在 M1 细胞中鉴定出一种特殊形式的对比度敏感性（对比度抑制），表明图案视觉信号在调节非成像视觉中的作用以及 M1 ipRGCs 在编码成像视觉线索中的潜在作用。该研究还揭示了一种由囊泡谷氨酸转运蛋白 3（vGluT3）无长突细胞介导的突触机制和视网膜回路，该机制是 M1 细胞对比度抑制反应的基础。研究还揭示了 M1 ipRGC 亚型（M1a 和 M1b），它们基于与 vGluT3 无长突细胞的突触连接、感受野特性、内在光敏感性和膜兴奋性以及形态特征而可区分，表明离散 M1 亚群之间存在视觉任务的划分。
已知 M1 型光感受器神经节细胞（ipRGC）可编码环境光信号，用于非成像视觉功能，例如昼夜光适应和瞳孔光反射。在这里，我们报告说，在小鼠视网膜中的 M1 细胞的一个亚群（M1a）具有被抑制的对比度（sbc）触发特性，这是一种先前仅在介导成像视觉的神经节细胞中发现的感受野特性。使用光遗传学和双膜片钳技术，我们发现囊泡谷氨酸转运蛋白 3（vGluT3）（vGluT3）无长突细胞特异性地形成甘氨酸能但不是谷氨酸能突触到 M1a 细胞上。M1a 细胞的视觉诱发反应的时空和药理学特性与 vGluT3 细胞的感受野特征非常吻合，这表明 vGluT3 无长突细胞输入在形成 M1a 细胞的 sbc 触发特性方面起着主要作用。我们发现，另一个 M1 细胞亚群（M1b）没有接收到直接的 vGluT3 细胞输入，因此缺乏 sbc 触发特性，在内在光反应、膜兴奋性、感受野特性和形态特征方面与 M1a 细胞明显不同。总之，结果揭示了一种视网膜回路，该回路使用 sbc 触发特性来调节辐照度编码，并可能将成像线索发送到大脑中的非成像视觉中心。
