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

小鼠 S1 皮质 L2/3 的神经编码组织和可塑性

• 批准号: 10653516
• 负责人: Daniel Feldman
• 金额: $ 47.45万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10653516
• 关键词: Anatomy; Attention; Attention deficit hyperactivity disorder; Basic Science; Biological Models; Calcium; Capsicum; Cells; Cerebral cortex; Code; Cues; Data; Detection; Equilibrium; Future; Image; Interneurons; Investigation; Learning; Maps; Measures; Modeling; Mus; Nature; Neighborhoods; Neurodevelopmental Disorder; Neurons; Output; Pattern; Performance; Property; Psychological reinforcement; Pyramidal Cells; Recording of previous events; Rewards; Rodent; Role; Sampling; Sensory; Site; Sodium Chloride; Somatosensory Cortex; Specificity; Stimulus; Structure; Testing; Vibrissae; attentional modulation; autism spectrum disorder; cognitive process; experience; flexibility; improved; neural; neural circuit; novel; optogenetics; response; segregation; selective attention; sensory cortex; two-photon; whisker discrimination

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.

概括 感官信息的非图形，混合表示（盐和点图）很常见 大脑皮层，但是如何在其中组织神经编码和可塑性。我们提出了这一点 盐和辣椒地图包含独特的锥体（Pyr）子网，在编码稳定性中具有不同的作用 和灵活性（包括学习和注意调制）。为了测试这一点，我们在层中研究晶须图 小鼠体感皮质（S1）的2/3，其中对柱状晶须（CW）调节的PYR细胞和非 - 柱状（非CW）晶须在每一列中都混合。我们最近发现非CW调谐细胞 在几天内显示出明显的调谐不稳定性，而CW调整的细胞具有稳定的调整。这表明 L2/3盐和胡椒地图有两个组件：稳定的CW调节单元的柱状柱地图，与 非CW调谐的细胞，这些细胞经过不及时的调节，几乎没有柱形地形。我们建议CW-和 非CW调谐细胞是不同的PYR子电路，在编码和可塑性中具有不同的作用。 这是S1电路函数的新型模型。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部位。根据初步数据，我们假设 非CW细胞中的调整不稳定性是内部驱动的，并且可以采取采样新型的感觉代码 然后通过经验或奖励来稳定。这是一个新颖的假设，说明感觉映射如何平衡稳定性 和可塑性 - 通过在不同的子电路中隔离这些功能。在AIM 1中，我们使用纵向2-Photon 钙成像以了解调整不稳定性的性质和起源，并测试经验还是 加固稳定晶须调节。在AIM 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。我们测试中央 假设非CW细胞是地图中感觉可塑性和学习的主要基因座。 AIM 3询问注意力如何调节被混合图中的神经编码。我们发展了一个选择性 注意任务，小鼠使用依赖历史的提示来指导注意特定晶须以改进 检测性能。小鼠对提示胡须表现出强烈的空间关注。注意持续约10秒，是 由最近将晶须刺激与奖励配对的驱动。初步数据表明注意力增强 晶须诱发的PYR细胞的活性编码S1中的晶须。这将S1确定为强大 研究皮层注意力的位点。我们将使用2光子成像和神经偶像记录 研究注意力如何调节S1中的感觉编码，包括测量大小和CW-或非CW 注意聚光灯的网络特异性。在重大努力中，我们使用成像和光遗传学来识别 控制电路在S1中引起注意，最初侧重于VIP中间神经元。 这些研究将共同​​揭示如何在A内组织可塑性和注意调制 规范的盐和胡椒地图。