Stimulus competition and visuospatial selection: Neural circuit and computational mechanisms

项目总结 动物通常在富含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突出(更广泛地说，是最优先的)刺激的指导来实现复杂性 环境。最高优先级刺激的竞争性选择背后的神经回路机制 对太空的了解仍然很少。最近有关猴子行为的证据表明， 上丘的中间和深层(SCID)，脊椎动物的主要感觉运动中枢 中脑是正常的竞争性刺激选择所必需的。同时，我们在谷仓猫头鹰视顶盖的工作 (OTid，SCID的鸟类同系物)揭示了OTid神经元明确地发出最高优先刺激的信号， 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一个 来自附近被称为IMC的抑制核团对OTid的空间抑制的特殊的、甜甜圈状的模式 中脑峡部复合体。另外，已知来自峡部胆碱能核(IPC)的反馈可以放大OTid 射击率。尽管有这些见解，关于这个地峡的功能逻辑的几个基本问题 (OT-IMC-IPC)竞争刺激选择网络仍然开放，在这里，我们解决三个问题。首先，我们的目标是 目的：阐明OTid中最显著刺激的优先神经信号是如何实现的。具体来说， 我们的假设是：(1a)OTid信号在相互竞争的刺激中是最强的， 伽马同步性、减少的试验-试验变异性、更强的适应性和降低的噪声相关性 (而不仅仅是随着激发频率的增加)，以及(1b)胆碱能IPC作为 管理这些不同的OTid编码特征。第二，我们的目标是阐明一种神经调节机制 分类的控制。我们的假设(基于我们的模型预测)是(2a)(迄今为止) 对IMC神经元的空间特异性胆碱能输入引起IMC的乘性调制 活跃性，以及(2b)它作为一种机制来增强最显著的 OTid的刺激。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，以及(3b)在 并行地，影响OT各层活动的IPC有选择地保留提供 输入到它(第10层)；展示了一种组织严密的电路设计，最大限度地减少了失控的反馈激励 在这个网络中。我们将使用体内电生理学和药物离子导入来验证这些假说 清醒、固定头部的谷仓猫头鹰的视觉刺激呈现，以及计算模型。初步 这三个目标的数据支持了我们的假设。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 复杂的计算是刺激竞争和空间选择的基础。

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.