Optical thalamic prosthesis analog for investigating V1 plasticity in blind adult mice

项目摘要 人们正在进行大量研究，以开发有效的神经修复装置来恢复失去的感觉。 然而，即使是在一个突出的成功的情况下，如人工耳蜗植入装置用于 虽然植入后听力恢复的可能性很小，但在以后的生活中进行植入时，结果可能会受到限制。这往往是 这归因于成年人大脑可塑性的降低。这是加剧的事实，即使与 尽管有最好的工程技术，神经假体设备还远远不能提供丰富的感觉信息 是由感觉器官产生的。这主要是由于电极接触点的数量有限， 而且还被在噪声背景中解码感觉信号的困难所困扰。因此 由感觉假体装置产生的神经活动通常被扭曲和退化 那些来自完整的感觉器官。为了让大脑有效地利用感觉假体产生的信息， 设备，它就变得至关重要，重新布线电路的失真信号的最佳处理。 失明可以由各种原因引起，但通常不涉及丘脑皮层回路，这可以用作 一种将人工信号从视觉假体传递到大脑皮层的基质。在这里，我们建议利用一本小说， 光学丘脑假体模拟，以检查失明成年小鼠的初级视觉皮层（V1）是否可以 重新配置以处理人工生成的信号。通过结合尖端的神经光子工具， 通过将光纤束耦合到GRIN（梯度折射率）开发了丘脑视觉假体模拟物 将透镜植入失明成年小鼠的视丘脑（dLGN，背外侧膝状体核）。激活 dLGN神经元使用光刺激，我们在dLGN神经元中表达了通道视紫红质变体。我们 有初步的数据表明，神经元在V1响应离散dLGN位置的光刺激。在这 我们的目标是测试V1在失明的成年小鼠中是否表达足够的可塑性以形成新的表征 基于从视丘假体模拟物产生的人工相关性。无论是失明的成年人 小鼠可以学会检测和区分这种丘脑激活的人工模式以指导行为。我们 工作可以扩展到检查从视丘产生的人工信号的参数 成人V1所需的假体类似物，以最佳地响应并产生可塑性，以及确定其 在指导盲人的自然行为方面的有用性。如果成功，我们的工作成果将 证明V1可塑性的程度和人工信号可能导致的习得行为， 有利于未来开发有效的视觉修复装置，以恢复失明成年人的视力。

Project Summary Much research is being done to develop effective neuroprosthetic devices to recover a lost sense. However, even in the case of a prominent success, such as the artificial cochlear implant devices used for recovering hearing, the outcome can be limited when the implantation is done later in life. This is often attributed to the reduced plasticity capacity of the adult brain. This is exacerbated by the fact that even with the best engineering efforts, neuroprosthetic devices are far from providing the rich array of sensory information that is generated by the sensory organs. This is largely due to the limited number of electrode contact points, but also confounded by the difficulties of decoding sensory signals amidst a noisy background. Thus, the neural activity generated by the sensory prosthetic devices are generally distorted and degraded compared to those from intact sensory organs. For the brain to effectively utilize information arising from sensory prosthetic devices, it then becomes essential to rewire the circuitry for optimal processing of the distorted signals. Blindness can result from various causes but usually spares the thalamocortical circuitry, which can be used as a substrate to convey artificial signals from visual prostheses to the cortex. Here we propose to utilize a novel optical thalamic prosthesis analog to examine whether the primary visual cortex (V1) of blind adult mice can be reconfigured to process artificially generated signals. By combining cutting-edge neurophotonic tools, we developed a thalamic visual prosthesis analog by coupling an optical fiber bundle to a GRIN (gradient index) lens implanted in the visual thalamus (dLGN, dorsal lateral geniculate nucleus) of blind adult mice. To activate dLGN neurons using photo-stimulation, we expressed a channelrhodopsin variant in the dLGN neurons. We have preliminary data that neurons in V1 responds to photo-stimulation of discrete dLGN locations. In this proposal, we aim to test whether V1 in blind adult mice express sufficient plasticity to form new representations based on artificial correlations generated from the optical thalamic prosthesis analog. And whether blind adult mice can learn to detect and discriminate such artificial patterns of thalamic activation to guide behavior. Our work can be extended to examine the parameters of the artificial signals generated from the optical thalamic prosthesis analog needed for adult V1 to respond optimally and produce plasticity, as well as determine its usefulness in guiding naturalistic behavior in blind adults. If successful, the results from our work will demonstrate the extent of V1 plasticity and learned behavior that can result from artificial signals, which can benefit future development of effective visual prosthetic devices for recovering vision in blind adults.