Department of Biology, University of Victoria, Victoria, Canada.
Danish Research Institute of Translational Neuroscience, Nordic-EMBL Partnership for Molecular Medicine, Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Elife. 2022 Nov 8;11:e81533. doi: 10.7554/eLife.81533.
The asymmetric summation of kinetically distinct glutamate inputs across the dendrites of retinal 'starburst' amacrine cells is one of the several mechanisms that have been proposed to underlie their direction-selective properties, but experimentally verifying input kinetics has been a challenge. Here, we used two-photon glutamate sensor (iGluSnFR) imaging to directly measure the input kinetics across individual starburst dendrites. We found that signals measured from proximal dendrites were relatively sustained compared to those measured from distal dendrites. These differences were observed across a range of stimulus sizes and appeared to be shaped mainly by excitatory rather than inhibitory network interactions. Temporal deconvolution analysis suggests that the steady-state vesicle release rate was ~3 times larger at proximal sites compared to distal sites. Using a connectomics-inspired computational model, we demonstrate that input kinetics play an important role in shaping direction selectivity at low stimulus velocities. Taken together, these results provide direct support for the 'space-time wiring' model for direction selectivity.
视网膜“星爆”型无长突细胞树突上的动力学不同谷氨酸输入的不对称总和是几种被提议的基础其方向选择性特性的机制之一，但实验验证输入动力学一直是一个挑战。在这里，我们使用双光子谷氨酸传感器（iGluSnFR）成像来直接测量单个星爆树突上的输入动力学。我们发现，与从远端树突测量到的信号相比，从近端树突测量到的信号相对持续。这些差异在一系列刺激大小中观察到，并且似乎主要由兴奋性而不是抑制性网络相互作用形成。时间反卷积分析表明，与远端部位相比，在近端部位的稳态囊泡释放率约大 3 倍。使用连接组学启发的计算模型，我们证明输入动力学在低刺激速度下对方向选择性起着重要作用。总之，这些结果为方向选择性的“时空布线”模型提供了直接支持。
