Local Connections and In Vivo Physiology of Inhibitory Cortical Neurons

项目摘要：尽管对皮层回路的基本蓝图有广泛的了解， 关于特定细胞类型的连通性以及它们如何发挥功能的研究仍然有限。这里提出的研究 将研究兴奋性和抑制性突触输入的层和细尺度特异性，以识别 抑制性神经元在大脑皮层，并将检查在体内生理学的具体抑制细胞类型 以及它们参与调节同步和振荡皮层活动。具体记录 抑制性细胞类型可以通过可视化限制于已知抑制性细胞的GFP表达来促进。 转基因小鼠的神经元类型。特定细胞类型的功能性输入的层特异性将是 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，相邻抑制细胞对之间的连接的精细尺度特异性， 兴奋性和抑制性细胞将通过诱发的突触反应的交叉相关分析来揭示 通过光刺激并从相邻对同时记录。此外，要了解在 特定抑制细胞类型的体内生理学和功能，在2- 将在表达GFP的转基因小鼠中从这些相同的细胞类型进行光子成像。我们将记录 从靶细胞的棘波，并通过皮层脑电图（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和尖峰触发相关的总体尖峰模式 将评估LFP的平均值，以确定 尖峰时间和皮层振荡记录的细胞的其他生理特性也将被描述。 评估以进一步了解抑制性神经元及其回路的特性。 相关性：涉及特定抑制细胞类型的皮质回路详细组织的研究， 这是理解大脑皮层功能的必要条件了解抑制性皮层的具体作用 神经元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 调节注意力的皮层机制及其中断与精神分裂症有关。

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.