Spatial and temporal precision of stimulus representation and processing in a highly disorganized cortex

新皮层的形态学特征之一是其组织为六个不同的层，由特定的细胞类型形成，具有特定的输入-输出关系。由此产生的连通性方案被认为强烈影响，如果不是决定，皮质功能。然而，皮层层是否确实是必要的，甚至是足够的，以确保适当的皮层功能，迄今为止还无法研究。在此，我们建议利用自然界的实验，即在reel小鼠中发现的reelin基因突变，来研究适当层的形成对皮质连通性和功能的影响。继上一个资助期的主题，即感觉刺激表征和处理，我们在这里扩展我们的研究，以识别兴奋性和抑制性神经元，以及通过半球相互作用的双边触觉信号处理。在精心设计的实验中，我们想要回答以下问题：(i) gaba能神经元是如何整合到（卷轴）体感皮层（高度混乱的）皮层回路中的？（ii）刺激双侧须如何影响皮层柱中感觉加工的整合？（iii）调解这种双边信号整合的电路机制是什么？我们将使用各种前沿技术，如体内双光子靶向膜片钳记录，与转基因动物杂交繁殖，体外光遗传学结合双全细胞记录和药理学操作以及所有记录神经元的严格形态学表征。通过这种方式，我们将首先了解来自端脑腹侧的抑制性中间神经元是如何整合到高度无序的新皮层中的。我们将开始研究通过胼胝体的感觉信号的半球间整合，这一过程对物体识别至关重要。我们还将剖析这种胼胝体回路的细胞类型特异性。通过将无组织皮层与正常皮层进行比较，我们相信，如果有的话，可以从这些实验中得出一个假定的层函数（Guy and Staiger, 2017）。

One of the morphological hallmarks of the neocortex is its organization into six distinct layers that, formed by specific cell types, possess specific input-output relationships. The resultant connectivity scheme is thought to strongly influence, if not determine, cortical functions. However, whether cortical layers are indeed necessary or even sufficient to ensure proper cortical function has so far been impossible to study. Here, we suggest to make use of an experiment of nature, i.e. the mutation of the reelin gene as being found in reeler mice, to study the influence of appropriate layer formation on cortical connectivity and function. Following up on the major theme of the previous funding period, which was sensory stimulus representation and processing, we here extend our studies to identified excitatory and inhibitory neurons, as well as to bilateral tactile signal processing through hemispheric interactions. In carefully designed experiment, by which a substantial number of new insights can be achieved for reeler but of equal importance also for wild type control animals, we want to answer the following questions: (i) How do GABAergic neurons integrate into the (highly disorganized) cortical circuits of (reeler) somatosensory cortex? (ii) How is bilateral whisker stimulation affecting integration of sensory processing in defined cortical columns? (iii) What are the circuit mechanisms that mediate this bilateral signal integration? We will use a variety of forefront techniques like in vivo two-photon-targeted patch clamp recordings, cross-breeding reeler with transgenic animals, in vitro optogenetics combined with dual whole cell recordings and pharmacological manipulations as well as rigorous morphological characterization of all recorded neurons. This way, we will get a first idea how inhibitory interneurons originating from the ventral telencephalon integrate into a highly disorganized neocortex. We will start to study interhemispheric integration of sensory signals via the corpus callosum, a process that is crucial for object identification. We will also dissect the cell type specificity of this callosal circuitry. By always comparing disorganized with normal cortex, we are confident that a putative function of layers, if there is any (Guy and Staiger, 2017), can emerge from these experiments.