Optical interrogation of laminar microcircuit computations in mouse primary visual cortex

小鼠初级视觉皮层层状微电路计算的光学询问

基本信息

  • 批准号:
    9977407
  • 负责人:
  • 金额:
    $ 3.88万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-09-01 至 2023-11-30
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract A fundamental challenge of visual cortical neuroscience is to understand how sensory representations are transformed within and across layers of primary visual cortex (V1). Visual signals are thought to propagate in a feedforward manner from the thalamus through the layered structure of V1, from L4 (L4) to layer 2/3 (L2/3) to layer 5. Here, we will address two major steps of visual processing: what are the mechanisms by which L4 transforms thalamic inputs, and how are representations transformed between L4 and L2/3? Recent studies in mouse V1 suggest that L4 amplifies thalamocortical inputs, but the mechanisms by which such amplification may occur, such as via local recurrent circuitry, have not been tested. Also, models from Hubel and Wiesel proposed that the formation of complex receptive fields in L2/3 arises from the combination of L4 simple cell inputs with similar orientation tuning and phase-offset subfields. Recent experimental work has shown preferential connectivity between L4 and L2/3 neurons that are co-tuned for different visual features, providing support for a potential mechanism by which selectivity is inherited. However, bridging the scales of anatomy and activity measurements to reveal cortical transformations has previously been challenging due to a lack of appropriate causal and functional methods. The goal of this proposal is to employ novel single-neuron resolution in vivo optical approaches for causally perturbing and monitoring neural activity to understand computations within and across layers during visual processing in awake animals. Our lab has developed a method, called influence mapping, for simultaneous two-photon optogenetic photostimulation of targeted individual neurons while imaging the responses of neighboring populations with known visual tuning properties. Aim 1 will use influence mapping in L4 of V1 to test the hypothesis that recurrent connectivity in L4 amplifies visual signals via a “like-excites-like” motif and determine whether such a motif is functionally operational for processing in different visual stimulus regimes (i.e., low vs. high contrast). The studies outlined in Aim 2 will directly test whether L2/3 complex receptive fields are built from L4 simple cell inputs by photostimulating functionally defined L4 neurons while imaging responses in L4 and L2/3. These experiments will advance our understanding of transformations within and between layers in visual cortex. In addition, the new technical approaches developed may serve as a foundation for future studies of laminar cortical mechanisms that underlie visual processing.
项目摘要/摘要 视觉皮层神经科学的一个根本挑战是理解感觉表征是如何 在初级视觉皮质(V1)的各层内和各层之间转换。视觉信号被认为是在一种 从丘脑通过V1的层状结构,从L4(L4)到L2/3(L2/3)到 第5层。在这里,我们将讨论视觉处理的两个主要步骤:L4通过什么机制 转换丘脑输入,以及L4和L2/3之间的表征如何转换?最近的研究 小鼠V1提示L4放大丘脑皮质的输入,但这种放大的机制 可能发生的情况,例如通过局部循环电路,尚未经过测试。此外,来自Hubel和Wiseel的模型 提出L2/3复杂感受野的形成源于L4简单细胞的结合 具有类似方向调谐和相位偏移子场的输入。最近的实验工作表明 L4和L2/3神经元之间的优先连接,这些神经元针对不同的视觉功能进行共同调节,提供 支持一种继承选择性的潜在机制。然而,将解剖学和 活动性测量揭示皮质变化之前一直具有挑战性,因为 适当的因果和功能方法。这项提议的目标是使用新的单神经元分辨 用于因果扰动和监测神经活动以理解计算的活体光学方法 在清醒动物的视觉处理过程中,层内和层间。我们的实验室已经开发出一种方法,叫做 影响图,用于同时对目标单个神经元进行双光子光遗传光刺激 同时成像具有已知视觉调谐特性的相邻群体的响应。AIM 1将使用 影响V1的L4的映射,以检验L4的反复连接通过 LIKE-EXCEPTES-LIKE模体,并确定这样的模体在功能上是否可用于在不同的 视觉刺激机制(即低对比度与高对比度)。目标2中概述的研究将直接测试L2/3 通过光刺激功能定义的L4神经元,从L4简单细胞输入建立复杂的感受野 同时成像L4和L2/3的反应。这些实验将促进我们对转换的理解 在视觉皮层的层内和层间。此外,开发的新技术方法可以作为一种 为未来研究作为视觉处理基础的层流皮质机制奠定基础。

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