FUNCTIONAL ANATOMY OF LOCAL CIRCUITS IN BARREL CORTEX

对大脑皮层局部回路的研究依赖于 单个神经元对刺激反应的生理学测量。 当前皮质功能研究方法中明显缺失的成分 是研究大群神经元正常功能的能力 一起工作。我们已经开发了一种实验程序， 首次使研究新陈代谢活动成为可能 神经系统中每个免疫组织化学标记的神经元 利息。该程序结合了高分辨率2-脱氧葡萄糖(2DG) 技术、谷氨酸脱羧酶(GAD)免疫染色等 抗原，以及广泛自动化的数据收集和分析。这些 材料允许直接评估激发程度和 对单个神经元的抑制作用。我们建议广泛利用 这种双标记技术用于研究胡须中的局部电路- 啮齿类动物躯体感觉皮层的相关桶状野。 我们将定量绘制和分析大脑皮质的细胞模式 在表现良好的仓鼠和小鼠身上可以看到2DG标记。我们会比较一下 来自正常的，尖锐的胡须修剪，人工刺激的皮质， 和长期修剪胡须的啮齿类动物相比 GAD和其他免疫染色的分布。我们将生成完整的 刺激和周围环境的高分辨率功能图 部分桶油田，从而能够准确地比较 在抗原定义的隔室中的代谢活动 大脑皮层。从这些地图所代表的数据库中，我们将测试一个 关于皮质功能和信息的具体假说的数量 在行为正常的动物的三叉神经系统中流动。 我们之前的2DG数据和预测的详细比较 尽管有很大的差异，但来自单个单位的生理学数据显示出良好的一致性 在这两种方法中。我们将通过寻找证据来追踪这条线 2DG/免疫染色材料与神经元功能群的相似性 这是其他工人的生理特征。我们会 然后用解剖学方法观察兴奋性和非兴奋性的投影场 神经元的抑制性群体，并将这些结果相互关联 在个体中采取激励和抑制程度的措施 具有不同组合的刺激胡须的神经元。我们会 评估皮质和皮质下环路的具体作用 通过比较不同站点的激活模式 面部留有胡须图案的三叉神经通路。 最后，我们将通过以下方法来表征桶形皮质的可塑性 皮质标记的正常模式与观察结果的比较 长时间剥夺胡须(修剪胡须)或人工胡须 刺激。

The study of local circuits in cerebral cortex has relied on physiological measures of the responses of single neurons to stimulation. The obvious missing ingredient in current approaches to cortical function is the ability to study the normal function of large groups of neurons working together. We have developed an experimental procedure which makes it possible, for the first time, to study the metabolic activity of every immunohistochemically labeled neuron in a neural system of interest. The procedure combines a high-resolution 2-deoxyglucose (2DG) technique, immunostaining for glutamate decarboxylase (GAD) and other antigens, and extensively automated data collection and analysis. These materials allow a direct assessment of the extent of excitation and inhibition in individual neurons. We propose to make extensive use of this double-labeling technology to study local circuitry in the whisker- related barrel field of rodent somatosensory cortex. We will quantitatively map and analyze the cellular patterns of cortical 2DG labeling seen in behaving hamsters and mice. We will compare cortices from normal, acutely whisker-trimmed, artificially stimulated, and chronically whisker-trimmed rodents with respect to the underlying distribution of GAD and other immunostains. We will generate complete high resolution functional maps of the stimulated and surrounding portions of the barrel field, enabling accurate comparison of the metabolic activities in antigenically defined compartments across the cortex. From the database represented by these maps, we will test a number of specific hypotheses about cortical function and information flow in the trigeminal system of the behaving animal. A detailed comparison of our previous 2DG data and predictions derived from single-unit physiology shows good agreement despite vast differences in the two methods. We will pursue this line of evidence by looking for parallels in 2DG/immunostained materials to functional groups of neurons that have been physiologically characterized by other workers. We will then examine by anatomical means the projection fields of excitatory and inhibitory populations of neurons, and correlate the results of these measures with the extent of excitation and inhibition in individual neurons with different combinations of stimulated whiskers. We will assess the specific contribution of cortical and subcortical circuitry by comparing the activation patterns in various stations of the trigeminal pathway with the patterns of whiskers remaining on the face. Finally, we will characterize the plasticity in barrel cortex by comparing the normal patterns of cortical labeling with those observed following prolonged deprivation (whisker trimming) or artificial whisker stimulation.