The role of inhibition in the mapping and plasticity of representations in V1

描述(由申请人提供)：兴奋和抑制之间的平衡对皮层回路功能至关重要，从而对大脑中表征的形成至关重要。此外，在从癫痫到自闭症和精神分裂症等神经疾病中也发现了失衡。皮质抑制性中间神经元是一类不同类型的细胞，它们对突触后神经元的定位不同，其形态和分子特征也不同。初级视觉皮质(V1)是研究皮层回路如何处理信息的一个很好的模型系统，因为简单的视觉刺激可以用来描述每个细胞的选择性反应特性。取向调节是V1中细胞的一个重要属性，但我们仍然不知道这种选择性是如何产生的。一种理论认为，皮质内连接是精炼这种选择性的关键，这种连接是由具有相似特性的细胞之间反复出现的兴奋性连接和抑制相互作用提供的，这些相互作用抑制了对所有方向的反应。我计划研究两种类型的抑制，即躯体靶向和树突靶向，是如何参与小鼠初级视觉皮质视觉表征的形成和维持的。我将使用最新可用的遗传方法来专门标记三种亚型的抑制细胞，即针对胞体的小白蛋白阳性(PV+)、针对树突的钙视黄素阳性(CR+)和针对树突的生长抑素阳性细胞(SOM+)。我预计这两种类型的抑制将显示出独特的定向属性，靶向SOMA的PV+细胞将具有尖锐的调谐，这将使它们能够提供高度特异性的前馈抑制，而针对CR+和SOM+细胞的树突将具有广泛或平坦的调谐，使它们能够增强定向调谐的对比度独立性。在这个项目的最后阶段，我将探索这些特定亚型细胞的可塑性，假设PV+细胞将表现出比其他两种细胞类型更高的短期可塑性水平。 与公共健康相关：这个项目将增加我们对兴奋和抑制之间平衡的特定方面如何有助于大脑回路准确处理信息的能力，以及这些回路如何适应环境变化的理解。这对于我们了解正常情况下的大脑功能至关重要，并将提高临床研究人员评估自闭症、精神分裂症和癫痫等疾病过程导致的皮质回路功能异常的能力。

DESCRIPTION (provided by applicant): The balance between excitation and inhibition is critical to cortical circuit function, and thus to the formation of representations in the brain. Furthermore, imbalances have been discovered in neurological disorders ranging from epilepsy to autism and schizophrenia. Cortical inhibitory interneurons are a diverse class of many distinct cell types, which differ in their anatomical targeting of the post-synaptic neuron, in their morphologies, and in their molecular signatures. The primary visual cortex (V1) is an excellent model system for studying how cortical circuits process information, because simple visual stimuli can be used to describe the selective response properties of each cell. Orientation tuning is an important property of cells in V1, but we still do not know how this selectivity arises. One theory is that intracortical connections, provided by recurrent excitatory connections between cells with similar properties and inhibitory interactions, which suppress responses to all orientations, are critical for refining this selectivity. I plan to study how two types of inhibition, soma-targeting and dendritic targeting, are involved in the formation and maintenance of visual representations in the primary visual cortex of the mouse. I will use newly available genetic approaches to specifically label three subtypes of inhibitory cells, soma-targeting parvalbumin-positive (PV+), dendrite-targeting calretinin-positive (CR+), and dendrite-targeting somatostatin- positive cells (SOM+). I expect that these two types of inhibition will demonstrate unique orientation properties, that soma-targeting PV+ cells will have sharp tuning, which would allow them to provide highly specified feedforward inhibition, and that the dendrite targeting CR+ and SOM+ cells will have broad or flat tuning, allowing them to enhance the contrast-independence of orientation tuning. In the final phase of this project, I will explore the plasticity of these specific subtypes of cells, with the hypothesis that PV+ cells will demonstrate higher levels of short-term plasticity than the other two cells types. PUBLIC HEALTH RELEVANCE: This project will increase our understanding of how specific aspects of the balance between excitation and inhibition contribute to the ability of brain circuits to accurately process information, and how these circuits adapt to change in the environment. This is critical to our understanding of brain function under normal conditions, and will improve the ability of clinical researchers to assess abnormalities in cortical circuit function that result from disease processes, such as autism, schizophrenia, and epilepsy.