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，因此对大脑表征的形成至关重要。此外，从癫痫到自闭症和精神分裂症等神经系统疾病也发现了失衡。皮层抑制性中间神经元是多种不同类型的细胞，它们在突触后神经元的解剖靶向、形态和分子特征上都有所不同。初级视觉皮层（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。定向调节是V1细胞的一个重要特性，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，由具有相似性质的细胞之间的周期性兴奋性连接和抑制性相互作用提供，抑制了对所有方向的反应，对于改进这种选择性至关重要。我计划研究两种类型的抑制，体细胞靶向和树突靶向，如何参与小鼠初级视觉皮层中视觉表征的形成和维持。我将使用最新的遗传方法来特异性标记三种亚型的抑制细胞，分别是体靶向parvalbuin阳性（PV+），树突靶向calretinin阳性（CR+）和树突靶向生长抑素阳性细胞（SOM+）。我期望这两种类型的抑制将表现出独特的取向特性，以体细胞为目标的PV+细胞将具有尖锐的调谐，这将使它们能够提供高度指定的前馈抑制，而以CR+和SOM+细胞为目标的树突将具有广泛或扁平的调谐，使它们能够增强取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+细胞将比其他两种细胞类型表现出更高的短期可塑性。

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.