Variability and robustness of functional neuronal properties in visual motion-detection circuitry

果蝇可以对不同的视觉刺激做出稳健的反应，但行为稳健的神经元基质和计算在很大程度上是未知的。果蝇核心运动检测电路的ON和OFF通路的神经元已被绘制。其中，Tm9神经元是OFF通路的视网膜位置排列的柱状中间神经元，并指导视运动行为。最近的研究表明，与其他Tm神经元不同，Tm9可以接收各种各样的突触前输入，这些输入的身份可能因个体Tm9神经元而异。我们的初步工作还揭示了一种非柱状、宽视场细胞类型与Tm9突触前的形态学和功能变异，即远端髓质神经元Dm4。此外，光学功能记录显示了相应的单个Tm9功能特性的变异性。这些发现提出了两个假说，需要在P5中进行验证：(1)可变的突触输入对于确定Tm9神经元的异质功能特性至关重要，(2)这反过来又是回路功能所必需的，并导致对挑战性刺激条件的行为稳健性。因此，P5的目标是了解突触前回路的不精确在多大程度上促进了对发育噪声的稳健性以及对可变视觉输入的功能稳健性。在该项目的两个平行部分，我们将首先量化和操作Tm9的可变突触前柱状电路架构，我们将分析Dm4宽场神经元作为Tm9的主要异质输入的贡献。为此，我们将把解剖学研究与苍蝇眼的生理测量相结合。我们将在基因上操纵变量输入，并测量Tm9生理以及对一系列视觉刺激的行为反应。当得出结论时，我们将测试不精确突触形成和异质性Tm9功能特性对运动检测在挑战性刺激条件下的鲁棒性的作用。

Flies can respond robustly to variable visual stimuli, but the neuronal substrate and computation underlying behavioral robustness are largely unknown. Neurons of the ON and OFF pathways of core-motion detection circuitry have been mapped in Drosophila. Of these, Tm9 neurons are retinotopically arranged columnar interneurons of the OFF pathway, and guide optomotor behavior. Recent work has shown that Tm9, unlike other Tm neurons, can receive a wide variety of presynaptic inputs, whose identity may differ for individual Tm9 neurons. Our preliminary work has also revealed morphological and functional variability in one non-columnar, wide-field cell type presynaptic to Tm9, the distal medulla neuron Dm4. Furthermore, optical functional recordings revealed a corresponding variability of individual Tm9 functional properties. These findings give rise to two hypotheses to be tested in P5: (1) variable synaptic inputs are essential to determine heterogeneous functional properties of Tm9 neurons, which (2) are in turn required for circuit function and lead to behavioral robustness to challenging stimulus conditions. Hence, the goal of P5 is to understand to what extent imprecisions in the presynaptic circuitry facilitates robustness to developmental noise as well as functional robustness to variable visual inputs. In two parallel parts of the project, we will first quantify and manipulate the variable presynaptic columnar circuit architecture of Tm9, and we will analyze the contribution of the Dm4 wide-field neuron as a major heterogeneous input to Tm9. To do so, we will combine anatomical studies with physiological measurements across the fly eye. We will genetically manipulate variable inputs and measure Tm9 physiology as well as behavioral responses to a range of visual stimuli. When concluded, we will have tested the role of imprecise synapse formation and heterogeneous Tm9 functional properties for the robustness of motion detection to challenging stimulus conditions.