Neural Circuits That Process Visual Information

项目概述：视觉丘脑中两个强大的抑制网络汇聚在中继细胞上 并影响下游的每一个尖峰局部中间神经元提供前馈抑制， 中继细胞和彼此。丘脑网状核接受来自中继细胞的输入并抑制它们 作为回报在固定组织或脑切片上的工作提供了对药理学、细胞生理学 和这些电路的解剖结构。显然有必要将这些离体结果应用于体内功能。到 为了弥补这一空白，我们直接从抑制细胞中记录并监测它们在中继细胞中产生的抑制 在视觉上。我们的策略更新了经典的比较解剖学和生理学方法， 将全细胞记录和细胞内标记与理论和计算技术相结合。 目的1）探索LGN中On和Off通路的整合。中继细胞有感受野 由同心开和关子区域组成，具有激励和抑制的推挽布局;例如， 明亮的刺激使人兴奋，黑暗使人抑制。视网膜提供推动（兴奋）。我们建议，拉（抑制 相反符号的刺激）来自局部的中间神经元，其感受野与它们的感受野相似。 突触后的合作伙伴，但与刺激极性相反的偏好。然而，很难绘制出 由于在大多数情况下，这些细胞不能在解剖学上区分， 哺乳动物因此，我们将通过使用雪貂来测试我们的假设，其中On和Off细胞占据不同的位置。 LGN的亚板层。目的2）在高等动物中探索抑制机制的模型系统。 遗传学方法使啮齿动物成为研究视觉的热门对象。然而，大脑皮层组织 食肉动物与啮齿动物的差异是巨大的，从功能结构的水平到单个 细胞我们通过定量地比较突触结构， 食肉动物与啮齿动物LGN的感受野。初步研究表明，处理的基本原则 在LGN中是保守的。因此，我们将使用缺乏On通道的突变体来探测推挽。此外，本发明还 猫的中间神经元和中继细胞以不同的方式处理它们的输入， 信息传递;我们将剖析啮齿动物中这些差异的基础。目标3）抑制性 对处理刺激对比度的贡献。我们假设推拉和同号抑制 （对优选刺激极性的抑制）扩大对刺激对比度的敏感性范围， 在高对比度下改进特征检测。我们将探讨视网膜外机制的对比度增益， 比较视网膜输入和丘脑输出模式的中继细胞和记录从中间神经元。推- 拉动抑制与同号抑制将通过使开启通道静默而凭经验分离，并且通过计算分离。 基于电导的模型。此外，我们将询问抑制如何通过以下方式促进特征选择性： 评估在不同对比下推和拉的相对权重的变化。

PROJECT SUMMARY: 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 cells 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 supplies 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 the 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 stimulus 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.