Microscale organization and sensory coding in L2_3 of mouse somatosensory cortex

 描述（由申请人提供）：大脑皮层中的神经回路如何平衡局部回路计算与中程和长程整合尚不清楚。一个强有力的例子是初级感觉皮层的层（L）2/3，其中局部网络接收来自其直接皮层柱的密集神经支配，以及跨柱、远端皮层-皮层、神经调节和其他输入。然而，目前还不清楚L2/3是否代表啮齿动物的非局部（整合）感觉功能，这是主要的动物模型皮层电路功能和疾病。该项目使用双光子群体钙成像，神经生理学和光遗传学来研究小鼠体感皮层（S1）L2/3的局部和综合感觉特征的神经编码，以及其内部和跨列的微观组织。大多数先前的工作在S1集中在表示非常本地，单须的感觉功能和它们的基础上，在intracolumnar本地电路。 在目标1中，我们证明，尽管强大的解剖柱状结构在S1，有一个高度分布的盐和胡椒微观组织的晶须感受野。我们量化了这种组织，测试了它在不同层次上的起源，并测试了自然胡须经验如何影响这种结构， 这种丰富的经验导致形成了地形上更精确的亚柱状地图。在目标2中，我们研究了L2/3中2-须序列（最简单的多须模式）的神经编码，并测试了一个新的假设，即序列表示如何在空间上组织在列内和跨列。在目标3中，我们测试是否突出的皮质-皮质输入到L2/3的S1从听觉和视觉皮层允许L2/3神经元获得跨模态（非晶须）的感觉反应在学习过程中。初步数据显示，在L2/3的S1的音调，预测奖励的音调反应的强大收购。我们描述了这种现象，测试单个S1神经元是否学会编码特定的非胡须刺激或奖励的一般期望，并使用光遗传学来测试这些学习的跨模态反应是否由来自其他感觉皮层的皮质-皮质投射介导。 总的来说，这些实验将揭示L2/3中新的整合功能和组织原则。了解S1中的这些特征将允许未来在自闭症和精神分裂症的小鼠模型中测试潜在的异常，这两种疾病可能反映了大脑皮层中局部兴奋性和长程整合之间的不平衡。

 DESCRIPTION (provided by applicant): How neural circuits in cerebral cortex balance local circuit computation with intermediate- and long-range integration is unclear. A powerful example is layer (L) 2/3 of primary sensory cortex, where local networks receive dense innervation from their immediate cortical column, as well as cross-columnar, distant cortico- cortical, neuromodulatory and other input. However, it remains unclear whether L2/3 represents nonlocal (integrative) sensory features in rodents, which are dominant animal models for cortical circuit function and disease. This project uses 2-photon population calcium imaging, neurophysiology, and optogenetics to study the neural coding of local and integrative sensory features in L2/3 of mouse somatosensory cortex (S1), and its micro-organization within and across columns. Most prior work in S1 has focused on representation of very local, single-whisker sensory features and their basis in intracolumnar local circuits. In Aim 1, we demonstrate that despite the strong anatomical columnar structure in S1, there is a highly distributed salt-and-pepper micro-organization of whisker receptive fields. We quantify this organization, test its origin across layers, and test how natural whisker experience affects this structure, with the surprising finding that enriched experience causes a more topographically precise subcolumnar map to form. In Aim 2, we study neural coding for 2-whisker sequences (the simplest multi-whisker pattern) in L2/3, and test a novel hypothesis for how sequence representation may be organized spatially within and across columns. In Aim 3, we test whether prominent cortico-cortical input to L2/3 of S1 from auditory and visual cortex allows L2/3 neurons to acquire cross-modal (non-whisker) sensory responses during learning. Preliminary data show robust acquisition of tone responses in L2/3 of S1 for tones that predict reward. We characterize this phenomenon, test whether individual S1 neurons learn to encode specific non-whisker stimuli or the general expectation of reward, and use optogenetics to test whether these learned cross-modal responses are mediated by cortico-cortical projections from other sensory cortices. Overall, these experiments will reveal novel integrative functions and organizational principles within L2/3. Understanding these features in S1 will allow future tests of potential abnormalities in mouse models of autism and schizophrenia, two disorders that may reflect an imbalance between local excitability and long- range integration in cerebral cortex.