Imaging neural networks in mouse somatosensory cortex

小鼠体感皮层神经网络成像

基本信息

批准号：
6654415
负责人：
JOSHUA Craig BRUMBERG
金额：
$ 11.23万
依托单位：
QUEENS COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-04-06 至 2004-03-31
项目状态：
已结题

项目摘要

The neocortex constitutes the largest component of the brain in mammals and is the primary site of mental functions. Crucial to its functionality are the interactions between distinct neuronal networks within the cortex. No unitary theory of how the cortex works exists, although it is clear that understanding its microcircuit is necessary to discern its computational capabilities. Anatomical and physiological studies have suggested that the connectivity of the cortical microcircuitry is complex, but not random. It is clear that inhibitory neurons target their connections extremely specifically. Less is known about the pyramidal-pyramidal connections that constitutes the `skeleton' of the cortex. A variety of anatomical and physiological experiments have highlighted the fact that there is heterogeneity among pyramidal cells in both their morphologies and response properties. It is conceivable that their interconnections are also precise and that the neocortex, like the retina, may be composed of dozens or hundreds of classes of neurons with specialized circuit functions. A major limitation of past work using traditional in vivo and in vitro recording techniques is the difficulty in revealing functional connections in large numbers. Furthermore, it is difficult to know with a high degree of certainty what type of neuron is being recorded from, for instance; is it a local circuit neuron or is it a cortical-fugal neuron? Finally, it is difficult to determine what network a specific neuron is incorporated within. These limitations have slowed our understanding of the connectivity patterns of the cortical microcircuit. To overcome these limitations fluorescent beads will be retrogradely transported back to independent networks of pyramidal cells located in layer VI of the primary somatosensory cortex, following injections into the ipsilateral motor cortex and/or the ventral posterior nucleus of the thalamus of mice. Fluorescent optics will facilitate the targeting of specific classes of neurons. Thalamocortical slices will be prepared from these animals for electrophysiological recordings and optical imaging of network activity using calcium indicators. By combining optical, fluorescent and electrophysiological techniques we will be able to both image the activity of an entire local circuit as well as record the activity of individual elements in the circuit during ongoing and stimulus driven network activity. The results of this study will further our understanding of the different classes of pyramidal cells and how they are connected as well as how the circuits anatomical connectivity affects is functionality. Gaining insight into the functioning of the cortical circuit can pave the way towards an understanding of fundamental physiological processes involved in information processing and how the disruption of the microcircuit by pathophysiological processes (e.g. schizophrenia) works, and thus possibly lead towards the development of new therapeutic interventions.

新皮层是哺乳动物中大脑最大的组成部分，是心理功能的主要部位。对其功能至关重要的是皮质内不同神经元网络之间的相互作用。尽管很明显，理解其微电路对于辨别其计算能力是必要的，但没有关于皮质的工作原理的统一理论。解剖学和生理研究表明，皮质微环路的连通性很复杂，但不是随机的。显然，抑制性神经元非常具体地针对其连接。关于构成皮层“骨骼”的锥体锥体连接的知之甚少。各种解剖学和生理实验都强调了这样一个事实，即在其形态和反应特性中，锥体细胞之间存在异质性。可以想象它们的互连也是精确的，并且像视网膜一样的新皮层可以由具有专门电路功能的数十种或数百种的神经元组成。使用传统体内和体外记录技术的过去工作的主要局限性是很难揭示大量功能连接。此外，很难在高度确定地记录哪种类型的神经元。它是局部电路神经元还是皮质 - 毛神经元？最后，很难确定在其中纳入了特定神经元的哪个网络。这些局限性使我们对皮质微电路的连通性模式的理解放缓。为了克服这些局限性，荧光珠将逆行运输到位于主要体感皮层第VI层的锥体细胞的独立网络，然后注射到小鼠Thalamus的同侧运动皮层和/或腹侧腹侧核。荧光光学元件将促进特定类别神经元的靶向。丘脑皮质切片将从这些动物中制备，以使用钙指标对网络活性进行电生理记录和光学成像。通过结合光学，荧光和电生理技术，我们将能够在正在进行和刺激驱动的网络活动期间记录整个局部电路的活性，并记录电路中各个元素的活性。这项研究的结果将进一步了解我们对不同类别的锥体细胞以及它们如何连接以及电路解剖连通性影响的方式是功能。洞悉皮质回路的功能可以为了解信息处理所涉及的基本生理过程以及如何通过病理生理过程（例如精神分裂症）造成微电路的破坏，从而为新的治疗干预措施的发展带来对微电路的破坏。