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.

新皮质是哺乳动物大脑的最大组成部分，也是心理功能的主要部位。其功能的关键是皮质内不同神经元网络之间的相互作用。尽管很明显，了解其微电路对于辨别其计算能力是必要的，但关于皮层如何工作的统一理论并不存在。解剖学和生理学研究表明，皮质微电路的连接是复杂的，但不是随机的。很明显，抑制性神经元非常明确地针对它们的连接。关于构成皮质“骨架”的锥体-锥体连接知之甚少。各种解剖学和生理学实验强调了这样一个事实：锥体细胞在形态和反应特性方面都存在异质性。可以想象，它们的互连也是精确的，并且新皮质与视网膜一样，可能由数十或数百类具有专门电路功能的神经元组成。过去使用传统体内和体外记录技术的工作的一个主要限制是难以揭示大量的功能连接。此外，很难高度确定地知道记录的是哪种类型的神经元；它是局部回路神经元还是皮质逃走神经元？最后，很难确定特定神经元包含在哪个网络中。这些限制减缓了我们对皮质微电路连接模式的理解。为了克服这些限制，荧光珠在注射到小鼠丘脑的同侧运动皮层和/或腹侧后核后，将逆行运输回位于初级体感皮层第六层的锥体细胞的独立网络。荧光光学将有助于瞄准特定类别的神经元。将从这些动物身上制备丘脑皮质切片，用于使用钙指示剂进行网络活动的电生理记录和光学成像。通过结合光学、荧光和电生理学技术，我们将能够对整个局部电路的活动进行成像，并在持续和刺激驱动的网络活动期间记录电路中各个元件的活动。这项研究的结果将进一步我们对不同类别的锥体细胞、它们如何连接以及电路解剖连接如何影响功能的理解。深入了解皮质回路的功能可以为理解信息处理中涉及的基本生理过程以及病理生理过程（例如精神分裂症）对微回路的破坏如何发挥作用铺平道路，从而可能导致新治疗方法的开发干预措施。