Neural Circuits That Process Visual Information

处理视觉信息的神经回路

• 批准号: 9139444
• 负责人: Judith A Hirsch
• 金额: $ 37.13万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9139444
• 关键词: Amblyopia; Anatomy; Animals; Architecture; Autistic Disorder; Biological Models; Brain; Cell Nucleus; Cell physiology; Cells; Code; Cognition; Computational Technique; Computer Analysis; Computer-Assisted Image Analysis; Computing Methodologies; Dendrites; Detection; Disease; Employee Strikes; Eye; Felis catus; Ferrets; Health; Hodgkin-Huxley model; Inherited; Interneurons; Joints; Label; Lateral Geniculate Body; Learning; Mammals; Maps; Membrane; Monitor; Mus; Output; Pathway interactions; Pattern; Pharmacology; Physiological; Physiology; Population; Primates; Process; Property; Retina; Retinal; Rodent; Schizophrenia; Shapes; Signal Transduction; Sleep; Slice; Stimulus; Strabismus; Structure; Study Subject; Subcellular Anatomy; Synapses; Testing; Thalamic structure; Travel; Update; Vision; Visual; Visual system structure; Weight; Whole-Cell Recordings; Work; base; comparative; genetic approach; genetic manipulation; improved; in vivo; information model; inhibitory neuron; insight; luminance; mouse model; mutant; neural circuit; postsynaptic; preference; receptive field; relating to nervous system; response; retinogeniculate; stimulus processing; theories; tissue fixing; transmission process; visual information

DESCRIPTION (provided by applicant): Two powerful inhibitory networks in the visual thalamus converge on relay cells and influence every spike that travels downstream. Local interneurons provide feedforward inhibition to relay cells and each other. The thalamic reticular nucleus receives input from relay cells and inhibits them in return. Work in fixed tissue or brain slices has provided insight into the pharmacology, cellular physiology and anatomy of these circuits. It is patently necessary apply these ex vivo results to function in vivo. To bridge this gap, we record from inhibitory cells directly and monitor the inhibition they generate in relay cels during vision. Our strategy updates classical comparative anatomical and physiological approaches by combining whole-cell recording and intracellular labeling in vivo with theory and computational techniques. Aim 1) Exploring the integration of On and Off pathways in the LGN. Relay cells have receptive fields made of concentric On and Off subregions with a push-pull layout of excitation and inhibition; e.g. where bright stimuli excite, dark inhibit. Retina supplie the push (excitation). We propose that the pull (inhibition to stimuli of the reverse sign) comes from local interneurons with receptive fields like those of their postsynaptic partners, but with te opposite preference for stimulus polarity. It is difficult, however, to map connectivity between and On and OFF cells because these cannot be anatomically distinguished in most mammals. Thus, we will test our hypothesis by using the ferret, where On and Off cells occupy different sublaminae in the LGN. Aim 2) Model systems to explore inhibitory mechanisms in higher animals. Genetic approaches make rodent a popular subject for studying vision. However, the cortical organization of carnivore vs. rodent is vastly different, from the level of the functional architecture to properties of single cells. We ask where these differences emerge by quantitatively comparing the synaptic structure of receptive fields in carnivore vs. rodent LGN. Preliminary studies suggest that basic principles of processing in the LGN are conserved. Thus, we will probe push-pull using mutants lacking an On channel. Further, interneurons and relay cells in cat process their inputs in quantitatively different ways that optimize information transmission; we will dissect the bases for these differences in rodent. Aim 3) Inhibitory contributions to processing stimulus contrast. We hypothesize that push-pull and same-sign inhibition (inhibition to the preferred stimulus polarity) expand the range of sensitivity to stimuus contrast and improve feature detection at high contrasts. We will explore extra-retinal mechanisms of contrast gain by comparing retinal input to thalamic output patterns in relay cells and by recording from interneurons. Push- pull vs. same-sign inhibition will be separated empirically by silencing the On channel, and computationally with conductance based models. In addition, we will ask how inhibition contributes to feature selectivity by assessing changes in the relative weights of push and pull at different contrasts.

描述（由申请人提供）：视觉丘脑中的两个强大的抑制网络会收敛于中继细胞，并影响下游传播的每个尖峰。局部神经元可提供对中继细胞和彼此的喂养抑制作用。丘脑网状核从中继细胞接收输入并抑制它们以换取。在固定组织或脑切片中的工作为这些电路的药理学，细胞生理和解剖结构提供了见解。显然有必要将这些离体结果应用于体内功能。为了弥合这一间隙，我们直接从抑制细胞记录下来，并监测它们在视力中产生的抑制作用。我们的策略通过将整个细胞记录和体内的细胞内标记与理论和计算技术相结合，从而更新了经典的比较解剖学和生理方法。目标1）探索LGN中开路和关闭路径的集成。继电器细胞具有由同心的接收场和关闭子区域制成的，具有推动的激发和抑制作用。例如明亮的刺激激发，深色抑制。视网膜提供了推动力（激发）。我们建议拉力（对反向刺激的抑制）来自局部中间神经元，其接收领域如其突触后伴侣的接收场，但对刺激极性的偏爱相反。但是，很难绘制细胞之间和关闭细胞之间的连通性，因为这些连通性在大多数哺乳动物中都无法解剖。因此，我们将通过使用雪貂测试我们的假设，在该假设中，在LGN中占据不同的sublaminae。目标2）模型系统探索较高动物的抑制机制。遗传方法使啮齿动物成为研究视力的流行主题。但是，食肉动物与啮齿动物的皮质组织与功能水平有很大不同 构建到单细胞的性质。我们通过定量比较食肉动物与啮齿动物LGN中接受场的突触结构来询问这些差异在哪里出现。初步研究表明，在LGN中加工的基本原理是保守的。因此，我们将使用缺乏ON通道的突变体进行探测推力。此外，猫中的中间神经元和中继细胞以数量不同的方式处理其输入，以优化信息传输；我们将剖析啮齿动物中这些差异的基础。目标3）对处理刺激对比的抑制作用。我们假设推拉杆和同一签名抑制（对优选刺激极性的抑制）扩大了对刺激对比度的敏感性范围，并在高对比度下改善了特征检测。我们将通过将视网膜输入与继电器细胞中的丘脑输出模式进行比较和通过中间神经元的记录来探讨对比增益的视网膜外机理。推拉与同一抑制作用将通过沉默的通道进行经验分开，并使用基于电导的模型进行计算。此外，我们将询问抑制如何通过评估以不同对比度推动和拉动的相对权重的变化来促进特征选择性。