Local Connections and In Vivo Physiology of Inhibitory Cortical Neurons

项目概述：尽管对大脑皮层回路的基本蓝图有广泛的了解，但详细的知识 关于特定细胞类型的连通性以及它们如何发挥作用的信息仍然有限。在这里提出的研究 将研究兴奋性和抑制性突触输入的层流和细微尺度特异性，以确定 大脑皮层中的抑制性神经元，并将在体内检测特定抑制性细胞类型的生理学 以及它们参与调节同步和振荡的皮质活动。录制特定的 抑制细胞类型可以通过将GFP表达限制为已知抑制细胞的可视化来促进 转基因小鼠的神经元类型。特定细胞类型的功能输入的层状特异性将是 通过使用将全细胞记录与扫描激光光刺激相结合的技术来理解。 此外，相邻的抑制性细胞对之间连接的细微尺度特异性或 通过对诱发的突触反应进行相互关联分析，将揭示兴奋性和抑制性细胞 通过光刺激并从相邻对同时记录。此外，要了解中的 体内特定抑制细胞类型的生理和功能，2-指导下的靶向记录 在表达GFP的转基因小鼠中，将对这些相同类型的细胞进行光子成像。我们将录制 并通过皮层脑电(ECoG)测量局部场电位(LFP) 录音。对于每种抑制性神经元类型，与LFP和Spietriggated相关的总体尖峰模式 将评估LFP的平均值以确定以下各项之间是否存在相关关系 尖峰时间和大脑皮层振荡。记录的细胞的其他生理特性也将 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如下 对于了解皮质功能是必要的。了解抑制性大脑皮层的具体作用 神经元对人类健康有重要的影响，因为这些细胞类型及其活动参与了 调节注意力及其干扰的大脑皮层机制与精神分裂症有关。

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 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 spiketriggered 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.