Imaging neural networks in mouse somatosensory cortex

小鼠体感皮层神经网络成像

• 批准号: 6324436
• 负责人: JOSHUA Craig BRUMBERG
• 金额: $ 10.72万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/6324436
• 关键词: bioimaging /biomedical imaging; biological models; brain imaging /visualization /scanning; calcium indicator; cell cell interaction; cell population study; charge coupled device camera; electrophysiology; fluorescence microscopy; fluorescent dye /probe; laboratory mouse; microcapsule; morphometry; neural information processing; neuroanatomy; neurons; neurophysiology; sectioning; somesthetic sensory cortex; stimulus /response; synapses; voltage /patch clamp

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.

新皮层是哺乳动物大脑中最大的组成部分，也是心理功能的主要部位。其功能的关键是皮层内不同神经网络之间的相互作用。尽管很明显，理解大脑皮层的微电路对于辨别其计算能力是必要的，但目前还没有关于大脑皮层如何工作的统一理论。解剖学和生理学研究表明，皮层微回路的连通性是复杂的，但不是随机的。很明显，抑制性神经元对它们之间的连接具有极强的特异性。人们对构成大脑皮层“骨架”的金字塔-金字塔连接知之甚少。各种解剖和生理实验都强调了锥体细胞在形态和反应特性上的异质性。可以想象，它们之间的相互联系也是精确的，而且新皮层和视网膜一样，可能由几十种或几百种具有特殊电路功能的神经元组成。过去使用传统的体内和体外记录技术的一个主要限制是难以揭示大量的功能连接。此外，很难高度肯定地知道记录的是哪一种神经元；它是局部回路神经元还是皮质-真菌神经元？最后，很难确定一个特定的神经元被整合在哪个网络中。这些限制减慢了我们对皮质微回路连接模式的理解。为了克服这些限制，将荧光珠注入小鼠同侧运动皮层和/或丘脑腹侧后核后，将其逆行运输回位于初级体感觉皮层第六层的独立锥体细胞网络。荧光光学将促进特定类别神经元的靶向。这些动物的丘脑皮质切片将用于电生理记录和使用钙指示剂对网络活动进行光学成像。通过结合光学、荧光和电生理技术，我们将能够对整个局部回路的活动进行成像，并在正在进行和刺激驱动的网络活动期间记录回路中单个元素的活动。本研究的结果将进一步加深我们对不同类型的锥体细胞及其连接方式的理解，以及电路解剖连接如何影响其功能。深入了解皮层回路的功能可以为理解涉及信息处理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起作用铺平道路，从而可能导致新的治疗干预措施的发展。