Stimulus competition and visuospatial selection: Neural circuit and computational mechanisms

刺激竞争和视觉空间选择：神经回路和计算机制

• 批准号: 10521981
• 负责人: Shreesh P Mysore
• 金额: $ 44.77万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10521981
• 关键词: Address; Anatomy; Animals; Area; Attention; Attention deficit hyperactivity disorder; Back; Barn Owls; Behavior; Birds; Brain; Categories; Cell Nucleus; Cells; Code; Complement; Complex; Computer Models; Data; Decision Making; Distant; Electrophysiology (science); Environment; Feedback; Functional disorder; Glutamates; Head; Homologous Gene; Injections; Iontophoresis; Logic; Mammals; Maps; Mental disorders; Methods; Midbrain structure; Monkeys; Muscarinics; Neurons; Neurotransmitters; Noise; Pattern; Perception; Process; Protocols documentation; Regulation; Resistance; Role; Route; Runaway; Schizophrenia; Sensory; Signal Transduction; Site; Source; Stains; Stimulus; Synapses; System; Tectum Mesencephali; Testing; Tracer; Visuospatial; Work; analytical tool; anatomical tracing; autism spectrum disorder; awake; base; cholinergic; cholinergic neuron; cholinergic synapse; design; experimental study; extracellular; in vivo; inhibitory neuron; insight; neural circuit; neuromechanism; neuroregulation; neurotransmission; novel; predictive modeling; prevent; receptive field; relating to nervous system; response; sensory stimulus; simulation; superior colliculus Corpora quadrigemina; visual stimulus

PROJECT SUMMARY Animals routinely operate in complex environments rich in sensory stimuli. They handle this informational complexity by having their behavior guided by the most salient (and more generally, highest priority) stimulus in the environment. The neural circuit mechanisms underlying competitive selection of the highest priority stimulus across space remain poorly understood. Recent evidence from behaving monkeys has revealed that the intermediate and deep layers of the superior colliculus (SCid), a major sensorimotor hub in the vertebrate midbrain, are required for normal competitive stimulus selection. In parallel, our work in the barn owl optic tectum (OTid, avian homolog of SCid) has revealed that OTid neurons signal the highest priority stimulus categorically, which can account for SCid’s critical role in spatial selection behavior. Such categorical signaling requires a specialized, donut-like pattern of spatial inhibition onto OTid from an inhibitory nucleus called Imc in the nearby midbrain isthmic complex. Separately, feedback from a cholinergic isthmic nucleus, Ipc, is known to amplify OTid firing rates. Despite these insights, several fundamental questions about the functional logic of this isthmo-tectal (OT-Imc-Ipc) network for competitive stimulus selection remain open, and here, we address three. First, we aim to elucidate how the preferential neural signaling of the most salient stimulus is implemented in OTid. Specifically, our hypotheses are (1a) that OTid signals the strongest among competing stimuli with a combination of enhanced gamma synchrony, reduced trial-trial variability, greater resistance to adaptation, and reduced noise correlations (rather than just with elevated firing rates), and (1b) that cholinergic Ipc serves as a multiplexed mechanism for regulating these diverse OTid coding features. Second, we aim to elucidate a neuromodulatory mechanism for the control of categorization. Our hypotheses (based on our model predictions) are (2a) that (hitherto uncharacterized) spatially-specific cholinergic input onto Imc neurons causes multiplicative modulation of Imc activity, and (2b) that it serves as a mechanism to enhance the degree of categorical signaling of the most salient stimulus by OTid. Third, we aim to uncover the source and broader functional logic of this cholinergic input. Our hypotheses are (3a) that Ipc is the dominant source of cholinergic input onto Imc neurons, and (3b) that in parallel, Ipc, which influences activity across the layers of the OT, selectively spares the OT layer that provides input to it (layer 10); revealing a precisely organized circuit design that minimizes runaway feedback excitation in this network. We will test these hypotheses using in vivo electrophysiology and drug iontophoresis during visual stimulus presentation in awake, head-fixed barn owls, together with computational modeling. Preliminary data from the three aims support our hypotheses. Results from the proposed work have the power to reveal fundamental neural circuit mechanisms involving multiple neurotransmitter systems for executing the sophisticated computations that underlie stimulus competition and spatial selection across space.

项目概要 动物通常在充满感官刺激的复杂环境中活动。他们处理这些信息 通过让他们的行为受到最显着（更普遍的是，最高优先级）刺激的指导来实现复杂性 环境。竞争性选择最高优先级刺激的神经回路机制 对跨空间的了解仍然知之甚少。最近来自猴子行为的证据表明， 上丘 (SCid) 的中间层和深层，是脊椎动物的主要感觉运动中枢 中脑是正常竞争性刺激选择所必需的。与此同时，我们对谷仓猫头鹰视顶盖的研究 （OTid，SCid 的鸟类同源物）表明 OTid 神经元明确地发出最高优先级刺激信号， 这可以解释 SCid 在空间选择行为中的关键作用。这种明确的信号需要 来自附近称为 Imc 的抑制核对 OTid 进行专门的、甜甜圈状的空间抑制模式 中脑峡部复合体。另外，已知来自胆碱能峡核 Ipc 的反馈会放大 OTid 发射率。尽管有这些见解，关于这个峡顶盖功能逻辑的几个基本问​​题 用于竞争性刺激选择的 (OT-Imc-Ipc) 网络仍然开放，在这里，我们讨论三个。首先，我们的目标是 阐明如何在 OTid 中实现最显着刺激的优先神经信号传导。具体来说， 我们的假设是 (1a) OTid 信号在竞争刺激中最强，并结合了增强 伽马同步、减少试验变异性、更大的适应阻力以及减少噪声相关性 （而不仅仅是提高放电率），以及 (1b) 胆碱能 Ipc 作为一种多重机制 调节这些不同的 OTid 编码功能。其次，我们的目标是阐明神经调节机制 分类控制。我们的假设（基于我们的模型预测）是（2a）（迄今为止） Imc 神经元上的未表征的空间特异性胆碱能输入导致 Imc 的乘法调制 活动，以及（2b）它作为一种机制来增强最显着的分类信号的程度 OTid 刺激。第三，我们的目标是揭示这种胆碱能输入的来源和更广泛的功能逻辑。我们的 假设 (3a) Ipc 是 Imc 神经元胆碱能输入的主要来源，(3b) 并行 IPC 会影响 OT 各层的活动，有选择地保留提供功能的 OT 层 输入到它（第10层）；揭示了精确组织的电路设计，可最大限度地减少失控反馈激励 在这个网络中。我们将使用体内电生理学和药物离子电渗疗法来测试这些假设 清醒、头部固定的仓鸮的视觉刺激呈现以及计算建模。初步的 来自三个目标的数据支持我们的假设。拟议工作的结果有能力揭示 涉及多个神经递质系统的基本神经回路机制，用于执行 复杂的计算是跨空间刺激竞争和空间选择的基础。