Borghuis Bart G, Looger Loren L, Tomita Susumu, Demb Jonathan B
Department of Ophthalmology and Visual Science, Department of Cellular and Molecular Physiology, and Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, Connecticut 06511, Department of Anatomical Sciences and Neurobiology, University of Louisville, School of Medicine, Louisville, Kentucky 40202, and Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, Virginia 20147.
J Neurosci. 2014 Apr 30;34(18):6128-39. doi: 10.1523/JNEUROSCI.4941-13.2014.
A fundamental question in sensory neuroscience is how parallel processing is implemented at the level of molecular and circuit mechanisms. In the retina, it has been proposed that distinct OFF cone bipolar cell types generate fast/transient and slow/sustained pathways by the differential expression of AMPA- and kainate-type glutamate receptors, respectively. However, the functional significance of these receptors in the intact circuit during light stimulation remains unclear. Here, we measured glutamate release from mouse bipolar cells by two-photon imaging of a glutamate sensor (iGluSnFR) expressed on postsynaptic amacrine and ganglion cell dendrites. In both transient and sustained OFF layers, cone-driven glutamate release from bipolar cells was blocked by antagonists to kainate receptors but not AMPA receptors. Electrophysiological recordings from bipolar and ganglion cells confirmed the essential role of kainate receptors for signaling in both transient and sustained OFF pathways. Kainate receptors mediated responses to contrast modulation up to 20 Hz. Light-evoked responses in all mouse OFF bipolar pathways depend on kainate, not AMPA, receptors.
感觉神经科学中的一个基本问题是，并行处理如何在分子和神经回路机制层面得以实现。在视网膜中，有人提出，不同类型的视锥细胞 OFF 双极细胞分别通过 AMPA 型和海人酸型谷氨酸受体的差异表达，产生快速/瞬态和慢速/持续通路。然而，在光刺激期间，这些受体在完整神经回路中的功能意义仍不清楚。在这里，我们通过对表达于突触后无长突细胞和神经节细胞树突上谷氨酸传感器（iGluSnFR）进行双光子成像，测量了小鼠双极细胞释放的谷氨酸。在瞬态和持续 OFF 层中，双极细胞由视锥细胞驱动释放的谷氨酸均被海人酸受体拮抗剂阻断，而未被 AMPA 受体拮抗剂阻断。对双极细胞和神经节细胞的电生理记录证实了海人酸受体在瞬态和持续 OFF 通路信号传导中的重要作用。海人酸受体介导了高达 20 Hz 的对比度调制响应。所有小鼠 OFF 双极通路中的光诱发反应均依赖于海人酸受体，而非 AMPA 受体。
