Organization of neural coding and plasticity in L2/3 of mouse S1 cortex

总结 感觉信息的非地形混合表示（盐和胡椒图）在 大脑皮层，但神经编码和可塑性是如何在其中组织尚不清楚。我们建议 椒盐图包含不同的金字塔（PYR）子网络，在编码稳定性方面具有不同的作用 灵活性（包括学习和注意力调节）。为了验证这一点，我们研究了层中的须图 2/3的小鼠躯体感觉皮层（S1），其中PYR细胞对柱状须（CW）和非柱状须（CW）进行调谐。 柱状（非CW）晶须在每列中混合。我们最近发现非连续波调谐细胞 显示出在几天内明显的调谐不稳定性，而CW调谐的细胞具有稳定的调谐。这表明， L2/3盐和胡椒图有两个组成部分：CW调谐细胞的稳定柱状图， 非CW调谐单元，其调谐不稳定并且具有很少的柱状形貌。我们建议CW-和 非CW调谐细胞是在编码和可塑性中具有不同作用的不同PYR子回路。 这是一种新的S1电路函数模型。我们预测CW网络提供编码稳定性， 而非CW细胞是可塑性和学习的主要场所。根据初步数据，我们假设 非CW细胞中的调谐不稳定性是内部驱动的，并用于采样新的感觉代码， 然后通过经验或奖励来稳定。这是一个关于感觉地图如何平衡稳定性的新假设 和可塑性-通过将这些功能分离在不同的子电路中。在目标1中，我们使用纵向双光子 钙成像，以了解调谐不稳定的性质和起源，并测试是否经验或 增强使晶须调谐稳定。在目标2中，我们评估CW和非CW网络是否代表 具有不同感觉编码和可塑性特性的不同功能网络。我们测试我们的中央 假设非CW细胞是地图内感觉可塑性和学习的主要场所。 目标3探讨注意力如何调节混合映射中的神经编码。我们开发了一种选择性的 注意力任务，其中小鼠使用历史依赖性线索来引导对特定胡须的注意力，以提高 检测性能老鼠对有线索的胡须表现出强烈的空间注意力。注意力持续~10秒， 由最近的胡须刺激与奖励的配对驱动。初步数据显示， 晶须诱发的活动PYR细胞编码出席晶须在S1。这使S1成为一个强大的 研究注意力皮层机制的网站。我们将使用双光子成像和Neuropixels记录， 研究注意力如何调节S1的感觉编码，包括测量大小和CW-或非CW 注意聚光灯的网络特异性。在一项重大的努力中，我们使用成像和光遗传学来识别 S1中的注意力控制回路，最初集中在VIP中间神经元上。 总之，这些研究将揭示可塑性和注意力调节是如何组织在一个 典型的椒盐地图

Summary Non-topographic, intermixed representations (salt-and-pepper maps) of sensory information are common in cerebral cortex, but how neural coding and plasticity are organized within them is unclear. We propose that salt-and-pepper maps contain distinct pyramidal (PYR) subnetworks with differential roles in coding stability and flexibility (including learning and attentional modulation). To test this, we study the whisker map in layer 2/3 of mouse somatosensory cortex (S1), where PYR cells tuned for the columnar whisker (CW) and for non- columnar (non-CW) whiskers are intermixed in each column. We recently discovered that non-CW tuned cells show marked tuning instability across days, while CW-tuned cells have stable tuning. This reveals that the L2/3 salt-and-pepper map has two components: a stable columnar map of CW-tuned cells, intermixed with non-CW tuned cells that are unstably tuned and have little columnar topography. We propose that CW- and non-CW tuned cells are distinct PYR subcircuits with different roles in coding and plasticity. This is a novel model of S1 circuit function. We predict that the CW network provides coding stability, while non-CW cells are the primary site for plasticity and learning. Based on preliminary data, we hypothesize that tuning instability in non-CW cells is internally driven, and acts to sample novel sensory codes which may then be stabilized by experience or reward. This is a novel hypothesis for how sensory maps balance stability and plasticity—by segregating these functions in different subcircuits. In Aim 1, we use longitudinal 2-photon calcium imaging to understand the nature and origins of tuning instability, and to test whether experience or reinforcement stabilizes whisker tuning. In Aim 2, we evaluate whether CW and non-CW networks represent distinct functional networks with different sensory coding and plasticity properties. We test our central hypothesis that non-CW cells are the primary locus of sensory plasticity and learning within the map. Aim 3 asks how attention modulates neural coding within intermixed maps. We developed a selective attention task in which mice use history-dependent cues to guide attention to a specific whisker to improve detection performance. Mice show robust spatial attention to cued whiskers. Attention lasts ~10 sec and is driven by recent pairing of whisker stimuli with reward. Preliminary data show that attention enhances whisker-evoked activity of PYR cells encoding the attended whisker in S1. This establishes S1 as a powerful site to study cortical mechanisms of attention. We will use 2-photon imaging and Neuropixels recording to study how attention modulates sensory coding in S1, including measuring the size and CW- or non-CW network specificity of the attentional spotlight. In a major effort, we use imaging and optogenetics to identify the control circuits for attention in S1, with initial focus on VIP interneurons. Together, these studies will reveal how plasticity and attentional modulation are organized within a canonical salt-and-pepper map.