The functional role of corticogeniculate feedback in vision

反馈中连接初级感觉皮质和初级感觉丘脑的皮质丘脑回路 方向在感觉通道和哺乳动物物种中无处不在，并且处于调节的理想位置 感觉信号从外周流向大脑皮层。然而，这些回路在感觉中的功能作用 感知仍然是神经科学中的一个基本谜团。在视觉系统中，皮质膝状体神经元 向膝状回背外侧核(LGN)的神经元提供大部分输入，无论其接受性如何 LGN神经元的视野与它们的视网膜输入非常相似，而不是它们的皮质膝状体输入。部分原因是 促肾上腺皮质激素对LGN活性的影响是调节的，而不是驱动的，其功能作用是 视觉中的皮质生成反馈一直很难描述。这项提议的首要目标是 阐明皮质膝状体反馈的结构组织及其在视觉知觉中的功能作用 行为。为了实现这一目标，采用了交叉和新兴技术，包括功能 超声成像、神经生理记录、光遗传学和化学遗传学 哺乳动物；雪貂和猕猴。基于我们之前的发现，皮质膝状体 反馈调节LGN对视觉输入的反应的时间和精度，这是这项研究的三个具体目标 提案涉及有关皮质膝状体反馈的功能和连通性的重要新问题。 具体目标1将检验皮质膝状体反馈是否调节LGN的时间动力学 神经元是独一无二的，这取决于它们传达的视觉特征信息的类型。《特定目标2》将考察 使用功能组合研究皮质激素对LGN种群活动的空间影响程度 超声波和光遗传学。目标2还将检查个体之间的精确功能连接 皮质膝状体和LGN神经元以确定皮质膝状体回路是否发挥流特异性 对单个LGN神经元的影响。具体目标1和2背后的一个主要动机是确定 皮质膝状体反馈调节流特异性LGN的视觉信息传输 或者皮质激素的影响是否更具全球性和扩散性。具体目标3代表了一个重要的 通过测试皮质激素环路如何影响皮质激素的功能，进一步了解皮质激素的功能 视觉辨别行为。我们已经开发出一种新的病毒介导的基因传递策略，能够 通过光遗传学或化学遗传学选择性地操纵皮质生成回路，适用于长期 在雪貂身上进行的行为实验。总之，在每个目标下提出的实验结果将提供一个 Fuller图通过揭示潜在的视觉感知，揭示皮质膝状体反馈在视觉感知中的功能作用 连通性和产生这些功能的机制。重要的是，关于皮质激素的见解 回路功能可以在整个感觉的皮质丘脑和皮质通路中泛化。 系统，并告知与许多神经系统疾病相关的感觉回路中断的理解。

Corticothalamic circuits linking the primary sensory cortex with the primary sensory thalamus in the feedback direction are ubiquitous across sensory modalities and mammalian species and are ideally positioned to regulate the flow of sensory signals from periphery to cortex. However, the functional role of these circuits in sensory perception remains a fundamental mystery in neuroscience. In the visual system, corticogeniculate neurons provide the majority of inputs onto neurons in the dorsal lateral geniculate nucleus (LGN), however receptive fields of LGN neurons closely resemble their retinal inputs and not their corticogeniculate inputs. Partly because corticogeniculate influence over LGN activity is modulatory rather than driving, the functional role of corticogeniculate feedback in vision has been difficult to characterize. The overarching goal of this proposal is to elucidate the structural organization of corticogeniculate feedback and its functional role in visual perceptual behavior. To accomplish this goal, intersecting and emerging technologies are employed including functional ultrasound imaging, neurophysiological recording, optogenetics, and chemogenetics in two highly visual mammalian species: ferrets and macaque monkeys. Building upon our previous findings that corticogeniculate feedback regulates the timing and precision of LGN responses to visual inputs, the three Specific Aims of this proposal address important new questions regarding the function and connectivity of corticogeniculate feedback. Specific Aim 1 will examine whether corticogeniculate feedback regulates the temporal dynamics of LGN neurons uniquely, depending on the type of visual feature information they convey. Specific Aim 2 will examine the spatial extent of corticogeniculate influence over LGN population activity using a combination of functional ultrasound and optogenetics. Aim 2 will also examine the precise functional connectivity between individual corticogeniculate and LGN neurons to determine whether corticogeniculate circuits exert stream-specific influence on individual LGN neurons. A major motivation behind Specific Aims 1 and 2 is to determine whether corticogeniculate feedback regulates visual information transmission through the LGN in a stream-specific manner or whether corticogeniculate influence is more global and diffuse. Specific Aim 3 represents a significant step forward in understanding corticogeniculate function by testing how corticogeniculate circuits contribute to visual discrimination behavior. We have developed a novel virus-mediated gene delivery strategy that enables selective manipulation of corticogeniculate circuits via optogenetics or chemogenetics, applicable to long-term behavioral experiments in ferrets. Together, results of the experiments proposed under each Aim will provide a fuller picture of the functional role of corticogeniculate feedback in visual perception by revealing the underlying connectivity and mechanisms giving rise to these functions. Importantly, insights gained about corticogeniculate circuit function could generalize across corticothalamic and corticocortical pathways throughout the sensory system and inform understanding of sensory circuit disruptions associated with many neurological disorders.