Neural Circuits That Process Visual Information

描述（由申请人提供）：视觉丘脑中的两个强大的抑制网络汇聚在中继细胞上，并影响下游的每个spike。局部中间神经元提供前馈抑制中继细胞和彼此。丘脑网状核接收来自中继细胞的输入并反过来抑制它们。对固定组织或大脑切片的研究为这些回路的药理学、细胞生理学和解剖学提供了深入的了解。显然有必要将这些离体结果应用于体内功能。为了弥补这一差距，我们直接记录抑制细胞并监测它们在视觉过程中在中继细胞中产生的抑制作用。我们的策略通过将全细胞记录和细胞内标记与理论和计算技术相结合，更新了经典的比较解剖学和生理学方法。目的1)探索LGN中On和Off通路的整合。继电细胞的接受野由同心圆的On和Off亚区组成，具有激发和抑制的推挽布局；明亮的刺激使人兴奋，黑暗的刺激使人抑制。视网膜提供推动（兴奋）。我们认为，拉力（对反向信号刺激的抑制）来自具有类似突触后伙伴的接受野的局部中间神经元，但对刺激极性的偏好相反。然而，绘制开关细胞之间的连通性是困难的，因为在大多数哺乳动物中，这些细胞在解剖学上无法区分。因此，我们将通过使用雪貂来验证我们的假设，其中打开和关闭细胞占据LGN的不同亚层。目的2)建立模型系统，探索高等动物的抑制机制。遗传方法使啮齿动物成为研究视觉的热门对象。然而，从功能水平来看，食肉动物和啮齿动物的皮层组织有很大的不同

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.