Functional circuitry and computation of the visual thalamus

项目总结/摘要 丘脑的背外侧膝状体核（dLGN）将视觉信号从眼睛路由到视觉中枢。 皮质，并为有意识的视觉提供关键支持。而不是一个简单的中继站， 越来越多的证据表明，小鼠dLGN在视觉信息的形成中起着积极的作用 通过选择性地汇聚和整合不同的输入流流向皮层。视网膜输入的研究 dLGN提供了关于神经回路的组织和发展的丰富知识， 哺乳动物物种。然而，关于非视网膜输入的了解少得多，尽管它们贡献了~90%。 的总输入到dLGN。非视网膜输入如何传递视觉和行为状态信息 结合来自视网膜的信息来影响丘脑的视觉处理仍然是一个很大的话题 实验和理论兴趣。清醒状态下dLGN输入的直接功能表征 在动物中进行高分辨率记录皮质下脑区域的困难阻碍了对动物的研究。 为了应对这一挑战，我们建立了一个慢性，高分辨率，脑深部双光子钙成像 该平台可以同时测量数百个视网膜轴突终扣的视觉反应。这里有 进一步扩大了我们的成像能力，同时记录来自两种不同钙指标的信号， 分别在视网膜和非视网膜输入中表达的颜色。通过这些创新，我们将确定 来自中脑上级丘的不同输入如何在多个水平上与视网膜输入协调， 增强或拓宽dLGN中的视觉信息通道。高度保守的丘膝状体轴突 具有几种类似于视网膜神经轴突的突触特性，包括混合轴突 在dLGN神经元的近端树突上的终扣，并提供强突触输入， 刺激目标神经元然而，仍然不清楚丘输入联合收割机如何与视网膜输入结合， 有助于dLGN神经元的视觉反应。在目标1中，我们将确定功能和空间 dLGN的视网膜和丘输入之间的关系。在目标2中，我们将揭示 通过行为状态来控制丘状体膝状体输入。在目标3中，我们将确定丘输入对 dLGN神经元的视觉反应。这些实验将揭示函数收敛的规则， 视网膜和丘的输入，并展示他们如何在音乐会或竞争中发挥作用，塑造丘脑视觉 计算我们的发现也将有助于理解传入视觉信号是如何转换的 研究dLGN中的视觉特征选择性以及行为状态如何影响这一过程，提供了基础 用于理解和治疗涉及神经回路连接不当的神经系统疾病， 信号集成

PROJECT SUMMARY/ABSTRACT The dorsal lateral geniculate nucleus (dLGN) of the thalamus routes visual signals from the eye to the visual cortex and provides critical support for conscious visual sensation. Rather than being a simple relay station, a growing body of evidence is revealing that the mouse dLGN plays an active role in shaping visual information flow to the cortex by selectively converging and integrating diverse streams of inputs. Studies of retinal inputs to the dLGN have provided rich knowledge about the organization and development of neural circuits for mammalian species. However, much less is known about the non-retinal inputs although they contribute to ~90% of total inputs to the dLGN. How the visual and behavioral state information conveyed by non-retinal inputs combines with information from the retina to impact thalamic visual processing remains a topic of great experimental and theoretical interest. Direct functional characterization of inputs to the dLGN in awake behaving animals has been hindered by the difficulty in performing high-resolution recording of subcortical brain regions. To address this challenge, we established a chronic, high-resolution, deep-brain two-photon calcium imaging platform to simultaneously measure visual responses in hundreds of retinal axonal boutons. Here, we have further expanded our imaging capacity to simultaneously record signals from calcium indicators of two different colors that are expressed in retinal and non-retinal inputs respectively. With these innovations, we will determine how the diverse inputs from the midbrain superior colliculus coordinate with retinal inputs at multiple levels to reinforce or broaden channels of visual information in the dLGN. The highly conserved colliculogeniculate axons possess several synaptic properties that resemble those of retinogeniculate axons, including comingling axonal boutons on the proximal dendrites of dLGN neurons and providing strong synaptic inputs that can elicit neural firing in target neurons. However, it remains unclear how the collicular inputs combine with retinal inputs and contribute to visual responses of dLGN neurons. In Aim 1, we will determine the functional and spatial relationships between retinal and collicular inputs to the dLGN. In Aim 2, we will reveal the modulation of colliculogeniculate inputs by behavioral states. In Aim 3, we will determine the contribution of collicular inputs to visual responses of dLGN neurons. These experiments will reveal rules for functional convergence between retinal and collicular inputs and demonstrate how they act in concert or in competition to sculpt thalamic visual computation. Our findings will also contribute to the understanding of how afferent visual signals are transformed into visual feature selectivity in the dLGN and how behavioral states impact this process, providing the foundation for the understanding and treatment of neurological disorders involving improper neural circuit connectivity and signal integration.