CRCNS: The balance of excitation and inhibition in sensory cortex

描述(申请人提供)：视觉皮质(V1)是神经元感受野特性发生戏剧性变化的地方--因此视觉世界的表现也在这里发生。其中一个主要的转变是出现了取向选择性。然而，V1中定向选择性的功能组织在不同物种中采取不同的形式。在灵长类和食肉动物中，它是在皮质上有地形组织的，而在啮齿动物中没有观察到明显的组织，但啮齿动物仍然表现出定向选择性。描述定向选择性出现的模型依赖于灵长类动物中发现的功能组织来指导共享选择性的神经元之间的连接。两种不同的假说被提出来解释啮齿动物V1中出现的无功能组织的定向选择性。在一种假设中，具有共同定向偏好的神经元之间的特定突触连接可能仍然存在，而不是皮质的地形组织。或者，一项计算研究表明，定向选择性可能来自非特定网络连接，约束条件是兴奋性和抑制性输入是平衡的(“平衡网络模型”)。这两个假说并不是相互排斥的，两个假说的证据目前都存在，但这些假说在多大程度上反映了啮齿动物V1中潜在的定向选择性的实际连接性尚不清楚。我们的建议的目的是通过实验和计算研究来解决平衡网络和特定的皮质连接对V1取向选择性产生的相对贡献。拟议的研究分为三个具体目标，将合作进行，并将整合理论 并进行实验。目标1：V1第4层的LGN输入的性质是什么？第4层如何转换此输入？在有方位图的物种中，LGN神经元的传入输入被精确排列。对于没有定位图的物种也是如此吗？皮质下的选择性如何影响皮质的选择性？我们能用一个平衡的网络来解释取向选择性的机制吗？目标2：大脑皮层的连接性是特定的吗？如果V1在平衡状态下运行，则无论连通性是否与特征有关，第2/3层都会出现很强的取向选择性。我们将测量输入相关性的方向依赖关系，并将任何特定的连接集成到一个平衡模型中。目标3：扰乱平衡状态如何影响皮质反应？我们的假设是，V1在平衡的兴奋和抑制状态下工作。扰乱这一平衡将从理论和实验两方面进行研究。尽管作为感觉处理的主要例子，V1已经研究了几十年，但人们对V1如何转换传入的视觉信息还不太清楚。例如，尚不清楚是否需要特定于功能的连接来执行其功能。对于有方位图的物种，特征特定的连通性与仅依赖解剖距离的连通性不容易区分，因为解剖图和功能图是联系在一起的。因此，啮齿动物V1缺乏定向选择性的解剖组织为我们提供了一个机会来研究神经元的功能选择性与其在皮质网络中的位置无关的系统中的回路。 我们的建议代表了理论家和实验者之间的综合合作，将为来自不同背景的学生和博士后研究员创造一个并肩工作的环境，获得不同的专业知识和视角。这项合作代表着法国和美国科学家合作的一项重大努力。这一合作关系将为来自法国和美国的学生提供在本国以外参与科学研究的机会。拟议的计算和实验实验室工作非常适合于培养具有物理、工程或生物背景的学生和博士后研究员。这将是一个极好的机会，让理论家看到并参与实验，并让实验者探索理论的观点。

DESCRIPTION (provided by applicant): Visual cortex (V1) is the site at which dramatic transformations in neuronal receptive field properties - and thus the representation of the visual world - occur. One of the major transformations is the emergence of orientation selectivity. The functional organization of orientation selectivity in V1, however, takes different forms across species. In primates and carnivores it is topographically organized across cortex but in rodents no apparent organization is observed, yet rodents still exhibit orientation selectivity. Models tha describe the emergence of orientation selectivity have relied on the functional organization found in primates to guide connectivity between neurons that share selectivity. Two different hypotheses have been proposed to explain the emergence of orientation selectivity without functional organization in rodent V1. In one hypothesis, a specific synaptic connectivity between neurons with shared orientation preference may nonetheless exist without topographic organization of cortex. Alternatively, a computational study has now demonstrated that orientation selectivity may arise from non-specific network connectivity, with the constraint that the excitatory and inhibitory inputs are balanced ("balanced network model"). These two hypotheses are not mutually exclusive, and evidence for both hypotheses currently exists, but the degree to which each of these hypotheses reflects the actual connectivity underlying orientation selectivity in rodent V1 is unclear. The goal of our proposal is to address the relativ contributions of the balanced network and specific cortical connectivity to the generation of V1 orientation selectivity using experimental and computational studies. The proposed research is divided into three Specific Aims that will be carried out collaboratively and will integrate theory and experiment. Aim 1: What is the nature of the LGN input into layer 4 of V1 and how does layer 4 transform this input? In species with an orientation map, the LGN neurons afferent inputs are precisely arranged. Is this also true for species without an orientation map, and how does subcortical selectivity impact cortical selectivity? Can we explain the mechanism for orientation selectivity using a balanced network? Aim 2: Is the cortical connectivity specific? If V1 operates in the balanced state, strong orientation selectivity will arise in layer 2/3, whether or not the connectivity is feature dependet. We will measure the orientation dependence of input correlations and integrate any specific connectivity into a balanced model. Aim 3: How does disturbing the balanced state affect the cortical response? Our hypothesis is that the V1 operates in balanced excitation and inhibition regime. Perturbing this balance will be investigated theoretically and experimentally. Despite decades of study as the prime example of sensory processing, how V1 transforms incoming visual information is not well understood. It is not clear for example, whether feature specific connectivity is required to perform its function. I species with an orientation map, feature specific connectivity is not easily distinguished from connectivity that is solely dependent on anatomical distance because the anatomical and functional maps are linked. The lack of an anatomical organization for orientation selectivity in rodent V1 therefore presents us with an opportunity to study circuitry in a system in which the functional selectivities of neurons are independent of their location within the cortical network. Our proposal represents an integrative collaboration between theoreticians and experimentalists that will create an environment for students and postdoctoral fellows from different background to work side-by-side, gaining access to distinct expertise and perspectives. The collaboration represents a major effort for scientists to work in partnership between France and the US. This partnership will provide students from both France and the US the opportunity to participate in science outside of their home country. The proposed computational and experimental lab work is ideal for the training of students and postdoctoral fellows with backgrounds in physics, engineering or biology. It will be an excellent opportunity for theorists t see and participate in experiments, and for experimentalists to explore a theoretical perspective.