CRCNS: Theory-guided studies of cortical mechanisms of multi-input integration

了解大脑、哺乳动物和人类的智力，以及了解 如何在遗传性和发育性疾病中出错，是为了理解 大脑皮层手术。关键的一步是理解大脑皮层进行的“规范”操作。这里 我们将在一个候选人的新理论的指导下，在实验中探索大脑皮层回路的操作 规范的电路操作。感觉皮质必须全局整合本地化的感觉输入以解析对象 并支持人们的看法。在单个神经元中，这表现为对局部刺激的反应通过 背景或自上而下的影响，如注意力和驾驶中局部刺激之间的相互作用 答复(“正常化”)。这些相互作用对较强的刺激往往是抑制的，但对较弱的刺激 对于较弱的刺激是抑制的或促进的。米勒博士实验室最近的理论工作提出了一种 新的大脑皮层回路基元，稳定的超线性网络(SSN)，提供了简单统一的 解释与全球一体化有关的各种神经反应。该模型作为一种 在Van Hooser博士的实验室中使用两种方法对皮质回路进行新的实验探索的指南 传统的实验记录技术和他最近开发的新的光学方法 以高空间和时间分辨率操纵大脑皮层活动。SSN模式如果成功，将 要详细说明，以便最好地解释实验结果。在目标1中，光激活通道视紫红质2 (ChR2)和光刺激系统用于在精确的空间和空间上驱动皮质电路的活动 测试皮层回路对正常化和上下文调制的贡献的时间模式 包括对它们的各种SSN预测。在目标2中，驱动力到兴奋性(E)与抑制性(E)的平衡 (I)皮质内的细胞将使用病毒改变，这种病毒在很大程度上将ChR2的表达限制在E或I细胞上。 这将测试SSN模型预测，该预测涉及通过调制输入偏置来调制网络增益 对于E或I细胞，注意调节的机制，以及“矛盾”结果的依赖-- 向I细胞添加驱动降低稳态I反应--关于驱动对I细胞和水平的空间模式 大脑皮层的激活。 相关性(请参阅说明)： 我们将测试一个强大的框架的预测，以了解全球感觉皮质 集成多种输入源，自下而上和自上而下，以产生神经元响应和 归根结底是感知。了解导致该皮质操作故障的电路变化可能 提供对自闭症和精神分裂症等障碍的洞察，这些障碍显示出背景或总体上的缺陷 正在处理。了解全球一体化对于创造治疗假体设备是必要的 失明和其他疾病。

A fundamental goal for understanding the brain and mammalian and human intelligence, and to understand how processing goes awry in genetic and developmental diseases, is to understand the principles of operation of cerebral cortex. A key step is to understand "canonical" operations carried out by cortex. Here we will explore the operations of cortical circuitry in experiments guided by a new theory of a candidate canonical circuit operation. Sensory cortex must globally integrate localized sensory input to parse objects and support perception. In individual neurons, this manifests as modulation of responses to local stimuli by context or top-down influences such as attention and as interactions between local stimuli in driving responses ("normalization"). These interactions tend to be suppressive for stronger stimuli but more weakly suppressive or facilitative for weaker stimuli. Recent theoretical work in Dr. Miller's lab has proposed a novel cortical circuit motif, the stabilized supralinear network (SSN), that provides a simple unified explanation for a wide variety of neural responses related to global integration. The model serves as a guide for new experimental explorations of cortical circuitry in Dr. Van Hooser's laboratory, using both traditional experimental recording techniques and his recently developed novel optical methods for manipulating cortical activity with high spatial and temporal resolution. The SSN model, if successful, will be elaborated to best explain experimental results. In Aim 1, the light-activated channel channelrhodopsin2 (ChR2) and an optical stimulation system are used to drive activity of cortical circuits in precise spatial and temporal patterns to test the contribution of cortical circuits to normalization and contextual modulation including various SSN predictions about them. In Aim 2, the balance of drive to excitatory (E) vs. inhibitory (I) cells within the cortex will be altered using viruses that largely restrict expression of ChR2 to E or I cells. This will test SSN model predictions involving modulation of network gain by modulatory input biased toward E or I cells, mechanisms of attentional modulation, and the dependence of a "paradoxical" result -­ adding drive to I cells reduces steady-state I responses -- on the spatial pattern of drive to I cells and level of cortical activation. RELEVANCE (See instructions): We will test the predictions of a powerful framework for understanding how sensory cortex globally integrates multiple sources of input, bottom-up and top-down, to produce neuronal responses and ultimately perception. Understanding circuit changes that cause breakdown of this cortical operation may provide insight into disorders such as autism and schizophrenia, which show deficits in contextual or global processing. Understanding global integration will be necessary for the creation of prosthetic devices to treat blindness and other disorders.