Neuronal ensembles in the rodent visual cortex

描述（由申请人提供）：我们计划解决两个关于大脑皮层回路的基本问题：“在皮层计算中，不同的神经元类别、锥体细胞和抑制性中间神经元的亚类的功能作用是什么？“自发活动的集合体的性质是什么？这些集合体与神经元的功能性质有什么关系？”我们将使用双光子钙成像的啮齿类动物在体内的视觉皮层，以测量所有神经元的方向选择性的体积层2/3（约500 5米的一侧，约10000个神经元）。如此完整地记录神经活动的前所未有的能力将增强我们对皮层回路两个方面的理解：细胞类别的多样性和自发活动的丰富性。我们将使用解剖学和遗传学技术来识别锥体神经元和各种类别的中间神经元。在没有感觉输入的情况下，使用双光子钙成像评估自发活动。在过去的几年里，不同神经元亚类的分子和细胞生理学分类取得了很大的进展。这些进展对神经功能的体内研究几乎没有影响，但现在具有单细胞分辨率的钙成像可以显示已通过遗传技术鉴定的神经元类别的功能相关性。大脑皮层中的自发活动已经有了很好的记录，但人们对其了解甚少。同时对整个神经回路进行细胞水平的监测对于推进这种相关活动及其与视觉功能的关系的研究至关重要。将使用宽场共振扫描系统，以便我们可以同时对三维体积中的数千个神经元进行成像。这种对整个局部回路功能的大规模概述将增强我们对健康和疾病中大脑皮层功能的理解。这种对大脑皮层子网络的基础研究直接适用于临床脑功能障碍。对公众健康影响最大的神经和精神疾病，如阿尔茨海默病、中风、癫痫、抑郁症和精神分裂症，都是皮层活动紊乱。本提案中概述的方法将以前所未有的完整性表征皮层回路;它们可用于研究正常大脑和神经系统疾病模型。

DESCRIPTION (provided by applicant): We plan to address two fundamental questions about cerebral cortical circuits: " What are the functional roles of different neuronal classes, pyramidal cells and subclasses of inhibitory interneurons, in cortical computations? " What are the properties of spontaneously active ensembles and how do these ensembles relate to the neurons' functional properties? We will use two-photon calcium imaging of the rodent visual cortex in vivo to measure the orientation selectivity of all neurons in a volume layer 2/3 (~500 5m on a side, ~10000 neurons). The unprecedented ability to record neural activity so completely will enhance our understanding of two aspects of cortical circuits: the diversity of cell classes and the richness of spontaneous activity. We will use anatomical and genetic techniques to identify pyramidal neurons and various classes of interneurons. Spontaneous activity will be assessed with two-photon calcium imaging in the absence of sensory input. Great advances have been made over the past several years on the molecular and cell- physiological classification of different neuronal subclasses. These advances have had little impact on in vivo studies of neural function, but now calcium imaging with single-cell resolution can show the functional correlates of classes of neurons that have been identified by genetic techniques. Spontaneous activity in the cerebral cortex has been well documented, but it is poorly understood. Simultaneous cellular-level monitoring of entire neural circuits is crucial for advancing the study of this correlated activity and its relation to visual function. A wide-field resonant-scanning system will be used so that we can image thousands of neurons in a three-dimensional volume simultaneously. This large-scale overview of the function of entire local circuits will enhance our understanding of cerebral cortical function in health and disease. This basic research on cortical sub-networks is directly applicable to clinical disorders of brain function. The neurological and psychiatric diseases with the largest impact on public health, Alzheimer's disease, stroke, epilepsy, depression and schizophrenia, are all disorders of cortical activity. The approaches outlined in this proposal will characterize cortical circuits with unprecedented completeness; they can be used to study both normal brains and models of neurological disease.