Local Connections and In Vivo Physiology of Inhibitory Cortical Neurons

描述(由申请人提供)：项目摘要：尽管对大脑皮层电路的基本蓝图有广泛的了解，但关于特定细胞类型的连接及其功能的详细知识仍然有限。本文提出的研究将研究兴奋性和抑制性突触输入大脑皮层已识别的抑制性神经元的层状和细微尺度的特异性，并将在体内检验特定抑制性细胞类型的生理学及其参与调节同步和振荡皮质活动的作用。在转基因小鼠中，绿色荧光蛋白(GFP)仅限于已知的抑制性神经元类型的表达，可以方便地记录特定的抑制性细胞类型。通过使用结合全细胞记录和扫描激光光刺激的技术，将了解特定细胞类型的功能输入的层状特异性。此外，相邻的抑制性细胞对或兴奋性和抑制性细胞之间的连接的细微尺度的特异性将通过光刺激引起的突触反应的相互关联分析来揭示，并同时从相邻的突触对记录下来。此外，为了了解特定抑制细胞类型的体内生理和功能，将在双光子成像的指导下，在表达GFP的转基因小鼠中对这些相同类型的细胞进行定向记录。我们将记录靶细胞的棘波，并通过皮层脑电记录测量局部场电位(LFP)。对于每种抑制性神经元类型，将评估与LFP和尖峰触发的LFP的平均值相关的总体尖峰模式，以确定尖峰时间和皮质振荡之间是否存在相关关系。记录的细胞的其他生理特性也将被评估，以进一步了解抑制性神经元及其电路的特性。相关性：对涉及特定抑制性细胞类型的皮质回路的详细组织的研究对于理解皮质功能是必要的。了解抑制性皮质神经元的具体作用对人类健康具有重要意义，因为这些细胞类型及其活动涉及调节注意力的皮质机制，并且它们的破坏与精神分裂症有关。

DESCRIPTION (provided by applicant): Project Summary: Despite extensive knowledge of the basic blueprint of cortical circuits, detailed knowledge about the connectivity of specific cell types and how they function is still limited. The studies proposed here will investigate the laminar and fine-scale specificities of excitatory and inhibitory synaptic input to identified inhibitory neurons in the cerebral cortex, and will examine in vivo physiology of specific inhibitory cell types and their participation in regulating synchronous and oscillatory cortical activities. Recordings of specific inhibitory cell types can be facilitated by visualization of green fluorescent protein (GFP) expression restricted to known inhibitory neuron types in transgenic mice. Laminar specificity of functional input to specific cell types will be understood by using the technique combining whole cell recordings with scanning laser photostimulation. Furthermore, the fine-scale specificity of connections between pairs of neighboring inhibitory cells or excitatory and inhibitory cells will be revealed by cross-correlation analyses of synaptic responses evoked by photostimulation and recorded simultaneously from the neighboring pairs. In addition, to understand in vivo physiology and function of specific inhibitory cell types, targeted recordings under the guidance of 2- photon imaging will be made from these same cell types in GFP-expressing transgenic mice. We will record spikes from the target cells and measure local field potentials (LFPs) through electrocorticogram (ECoG) recordings. For each inhibitory neuron type, the overall spiking pattern in relation to LFPs and spike- triggered average of LFPs will be assessed to determine whether a correlative relationship exists between spike times and cortical oscillations. Other physiological properties of the recorded cells will also be assessed to further understand the properties of inhibitory neurons and their circuits. Relevance: Studies of the detailed organization of cortical circuits involving specific inhibitory cell types are necessary toward understanding cortical function. Understanding the specific roles of inhibitory cortical neurons has important implications for human health, as these cell types and their activities are involved in the cortical mechanisms that regulate attention and their disruption is implicated in schizophrenia.