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

用于研究失明成年小鼠 V1 可塑性的光学丘脑假体模拟

• 批准号: 10592670
• 负责人: Hey-Kyoung Lee
• 金额: $ 24.56万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10592670
• 关键词: Adult; Auditory Perception; Behavior; Behavioral Paradigm; Biological; Blindness; Brain; Cochlear Implants; Coupled; Coupling; Data; Development; Devices; Discrimination; Dorsal; Effectiveness; Electrodes; Engineering; Fiber Optics; Future; Head; Hearing; Image; Implant; Individual; Lateral Geniculate Body; Learning; Life; Light; Location; Mus; Neurons; Ocular Dominance; Ocular Prosthesis; Optic Nerve; Optics; Organ; Outcome; Pattern; Preparation; Process; Prosthesis; Recovery; Research; Retina; Sensory; Signal Transduction; Source; Speech Perception; Structure; System; Testing; Thalamic structure; Tissues; V1 neuron; Variant; Vision; Visual; Visual Cortex; Work; analog; area striata; behavior test; blind; deaf; digital; implantable device; implantation; indexing; interest; learned behavior; lens; neural; neural correlate; neuroprosthesis; neurotransmission; novel; optical fiber; optogenetics; sensory cortex; sensory prosthesis; success; tool; two-photon

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.

项目概要 人们正在进行大量研究来开发有效的神经假体装置来恢复失去的感觉。 然而，即使取得了显着的成功，例如用于人工耳蜗植入装置 恢复听力，当晚年进行植入时，结果可能会受到限制。这常常是 归因于成人大脑的可塑性能力降低。即使有 尽管尽了最大的工程努力，神经假体设备还远远不能提供丰富的感官信息 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， 但也因在嘈杂的背景下解码感官信号的困难而感到困惑。因此， 与其他感觉假肢装置相比，由感觉假肢装置产生的神经活动通常会被扭曲和退化。 来自完整感觉器官的那些。让大脑有效利用感觉假体产生的信息 设备，然后必须重新布线电路以优化失真信号的处理。 失明可能由多种原因引起，但通常不会影响丘脑皮质回路，该回路可用作 将人工信号从视觉假体传递到皮层的基质。在这里我们建议利用小说 光学丘脑假体类似物，用于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，我们 通过将光纤束耦合到 GRIN（梯度指数）开发了丘脑视觉假体模拟 晶状体植入失明成年小鼠的视觉丘脑（dLGN，背外侧膝状核）。激活 使用光刺激 dLGN 神经元，我们在 dLGN 神经元中表达视紫红质通道蛋白变体。我们 初步数据表明 V1 中的神经元对离散 dLGN 位置的光刺激有反应。在这个 建议，我们的目的是测试成年失明小鼠的 V1 是否表现出足够的可塑性以形成新的表征 基于光学丘脑假体模拟生成的人工相关性。以及是否盲人成人 小鼠可以学会检测和区分丘脑激活的这种人工模式以指导行为。我们的 工作可以扩展到检查光学丘脑产生的人工信号的参数 成人 V1 需要的假体类似物才能做出最佳反应并产生可塑性，并确定其 在指导盲人成年人的自然行为方面很有用。如果成功的话，我们的工作成果将 展示 V1 可塑性的程度以及由人工信号产生的学习行为，这可以 有利于未来开发有效的视觉假肢设备，以恢复盲人成年人的视力。