Circuit function and visual signal processing in the retina

我们的工作集中在内部视网膜的专门电路。在详细研究了几种视网膜内突触的生理学特征之后，我们现在试图了解这些突触如何在周围的视觉处理回路中发挥作用。 我们已经仔细研究了杆通路，特别是突触输入和输出A2无长突细胞。其他实验室最近的研究表明，向A2提供兴奋性输入的杆状双极细胞（RBC）主要从其他RBC驱动的宽场GABA能无长突细胞接受突触前抑制。我们假设这种环绕抑制调节RBC-A2信号的增益和动态范围，使A2能够在中暗视觉范围内有效地整合信号。我们已经记录了视觉诱发信号在A2中的黑暗适应的整装视网膜准备检查这种反馈抑制视觉信号的影响。我们的研究结果表明，这种反馈抑制调节突触信号在中间和明视条件下，但不是在非常低的光（暗视）水平。进一步的实验表明，nNOS-1无长突细胞介导的反馈抑制在中间视觉条件下，但一些其他的无长突细胞在更高的光水平的贡献。 我们正在继续研究小鼠视网膜中的星爆无长突细胞（SAC）功能，方法是采用机器学习方法来识别ChAT-tdTomato小鼠视网膜中荧光过程密集丛内的单个SAC。我们已经成功地开发出一种算法，分割单个神经元从一个领域包含其他几个重叠的SAC。实验室的一名研究生正在将这种方法扩展到其他细胞类型。已提交了一份手稿，并邀请进行修订。 我们也正在研究一种新的机制，通过这种机制，一种单一的、密集表达的无长突细胞类型可能提供了光诱发活动和视网膜血管控制之间的联系。我们结合电生理，成像和connectomic的方法来检查电路的连接和功能的无长突细胞。这些细胞通过与Muller神经胶质细胞的连接与脉管系统相互作用。我们最近完成了一个详细的系列EM形态学分析的穆勒细胞，揭示了以前不受重视的安排穆勒细胞相对于视网膜血管。成像实验揭示了中间血管层毛细血管周围的Muller过程中的钙信号。手稿正在准备中。实验正在进行中，以检查这种有趣的形态的生理后果。

Our work focuses on specialized circuitry in the inner retina. Having examined several inner retinal synapses in physiological detail, we now seek to understand how these synapses contribute to visual processing in the surrounding circuitry. We have studied closely the rod pathway, specifically the synaptic inputs to and outputs from A2 amacrine cells. Recent work from other labs has shown that rod bipolar cells (RBC), which provide excitatory input to A2s, receive presynaptic inhibition primarily from a wide-field GABAergic amacrine cell driven by other RBCs. We hypothesize that this surround inhibition modulates the gain and dynamic range of RBC-A2 signaling, enabling the A2 to integrate signals effectively in the mid-scotopic visual range. We have recorded visually evoked signals in A2s in the dark-adapted whole-mount retina preparation to examine the effects of this feedback inhibition on visual signaling. Our results indicate that this feedback inhibition modulates synaptic signaling under mesopic and photopic conditions, but not under very low light (scotopic) levels. Further experiments indicate that nNOS-1 amacrine cells mediate feedback inhibition under mesopic conditions but that some other amacrine cell contributes at higher light levels. We are continuing our examination of starburst amacrine cell (SAC) function in the mouse retina by undertaking a machine learning approach to identifying individual SACs within the dense plexus of fluorescent processes in the ChAT-tdTomato mouse retina. We have successfully developed an algorithm to segment individual neurons from a field containing several other overlapping SACs. A graduate student in the lab is extending this approach to other cell types. A manuscript was submitted and a revision has been invited. We are also examining a novel mechanism by which a single, densely expressed amacrine cell type may provide the link between light evoked activity and control of the retinal vasculature. We have combined electrophysiogical, imaging and connectomic approaches to examine the circuit connectivity and function of this amacrine cell. These cells interact with the vasculature via connections with Muller glial cells. We have recently completed a detailed serial EM morphological analysis of Muller cells that has revealed previously unappreciated arrangements of Muller cells with respect to the retinal vasculature. Imaging experiments reveal calcium signals in Muller processes surrounding capillaries in the intermediate vascular layer. A manuscript is in preparation. Experiments are underway to examine physiological consequences of this interesting morphology.