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

点击翻译按钮获取中文摘要

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.