SYNAPTIC ORGANIZATION AND VISUAL PROCESSING IN INTERNEURON CIRCUITS OF THE RETINA

在神经系统的许多部分，负责调节回路内局部相互作用的中间神经元 与投射神经元不同，投射神经元在一条通路中的后续电路之间传递信息。截止日期： 这种多样性的一部分，许多中间神经元的功能是未知的和一般的操作原理 神经元间回路尚待确定。中间神经元的多样性可能在视网膜最大，在那里 大约40种不同类型的无长突细胞(AC)与双极细胞形成特定的连接模式， 它们将光感受器信号从视网膜外部传递到内部，以及视网膜神经节细胞，它们将 视网膜信息传给大脑。大多数AC类型释放GABA或甘氨酸，许多类型释放兴奋性 神经递质或神经调质(即双重递质神经元)，进一步增强了 他们的信号。在这里，我们将分析特定的AC类型对视网膜和 到由不同形式的视觉运动引起的特征行为。在此过程中，我们将测试一组通用的 原则(即功能模块化)，我们假设这些原则支配交流电路的运行。我们最近 研究发现，表达VGluT3的ACS(VG3-ACS)是视网膜中的局部运动检测器 为对象运动敏感神经节细胞提供兴奋性输入。该电路的选择性依赖于FAST 抑制输入，取消对全局运动刺激的反应。目前提供此输入的交流类型(S)是什么 未知。初步结果表明，两种遗传鉴定的广域AC类型形成抑制性连接 对物体运动敏感的神经节细胞。在目标1中，我们将测试其中一种或两种交流类型是否会抑制额外的 此回路兴奋轴的层数(即双极细胞，VG3-ACS)。然后我们将使用小鼠，在这些小鼠中 暂时或稳定地沉默，或从成熟的视网膜上移走，以探索其功能贡献 对象运动敏感电路中的运动处理的输入。此外，我们还将评估它们对 引导小鼠对局部运动刺激的反应。光遗传学实验表明，VG3-ACS提供了 对其他神经节细胞类型的兴奋性输入，具有明显的运动偏好。是否发生此输入 在视觉过程中，以及VG3-ACS如何在这些电路中促进运动处理和影响特性 由不同形式的视觉运动引起的行为尚不清楚。在目标2中，我们将测试功能意义 VG3-ACS兴奋性传入不同运动敏感神经节细胞的解剖学基础及评价 VG3-ACS暂时或稳定沉默的小鼠对视觉运动的行为反应的变化， 或者从成熟的视网膜中取出。有趣的是，初步结果表明，VG3-ACS提供了选择性 被运动抑制的神经节细胞的抑制性输入。我们将分析它们的模式和功能 连接并测试这种特定于目标的使用双发射机对抑制反应的贡献 这些神经节细胞。

In many parts of the nervous system, interneurons, which mediate local interactions within a circuit, are more diverse than projection neurons, which transmit information between subsequent circuits in a pathway. Due in part to this diversity, the functions of many interneurons are unknown and general operating principles of interneuron circuits remain to be identified. The diversity of interneurons may be greatest in the retina, where approximately 40 distinct types of amacrine cells (ACs) form specific patterns of connections with bipolar cells, which transmit photoreceptor signals from the outer to the inner retina, and retinal ganglion cells, which transmit retinal information to the brain. Most AC types release GABA or glycine, and many release excitatory neurotransmitters or neuromodulators as well (i.e. dual transmitter neurons), further enhancing the diversity of their signals. Here, we will analyze the contributions of specific AC types to motion processing in the retina and to characteristic behaviors elicited by different forms of visual motion. In doing so, we will test a set of general principles (i.e. functional modularity), which we hypothesize govern the operation of AC circuits. We recently identified VGluT3-expressing ACs (VG3-ACs) as local motion detectors in the retina, and showed that VG3-ACs provide excitatory input to object motion sensitive ganglion cells. The selectivity of this circuit relies on fast inhibitory inputs that cancel responses to global motion stimuli. Which AC type(s) provide this input is currently unknown. Preliminary results show that two genetically identified wide-field AC types form inhibitory connections with object motion sensitive ganglion cells. In Aim 1, we will test whether either or both AC types inhibit additional tiers of the excitatory axis of this circuit (i.e. bipolar cells, VG3-ACs). We will then use mice in which these ACs are transiently or stably silenced, or are removed from mature retinas, to probe the functional contribution of their input to motion processing in the object motion sensitive circuit. In addition, we will assess their influence on orienting responses of mice to local motion stimuli. Optogenetic experiments suggest that VG3-ACs provide excitatory input to additional ganglion cell types, with distinct motion preferences. Whether this input occurs during vision, and how VG3-ACs contribute to motion processing in these circuits and influence characteristic behaviors elicited by different forms of visual motion is unclear. In Aim 2, we will test the functional significance and anatomical basis of excitatory input from VG3-ACs to different motion sensitive ganglion cells and assess changes in behavioral responses to visual motion in mice in which VG3-ACs are transiently or stably silenced, or are removed from mature retinas. Intriguingly, preliminary results indicate that VG3-ACs provide selective inhibitory input to a ganglion cell that is suppressed by motion. We will analyze the patterns and function of these connections and test the contribution of this target-specific use of dual transmitters to suppressive responses of these ganglion cells.