Time delimited neural silencing to dissect the basis of visual object perception

时间限定的神经沉默来剖析视觉对象感知的基础

基本信息

批准号：
8609040
负责人：
James J DiCarlo
金额：
$ 19.11万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-02-01 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8609040
关键词：
Acute Affect Animals Area Behavioral Brain Cereals Code Complex Data Dependence Development Devices Disease Dissection Electrodes Experimental Designs Face Feedback Functional Magnetic Resonance Imaging Goals Health Image Inferior Injection of therapeutic agent Intervention Lead Light Location Magnetic Resonance Imaging Maps Measurable Methods Microinjections Muscimol Nature Neocortex Neurons Optics Outcome Personal Satisfaction Primates Process Quality of life Reaction Time Resolution Role Signal Transduction Site Stream System Task Performances Techniques Temporal Lobe Testing Time Tissues Viral Vision Visual Visual Cortex Work awake base behavior test implantation light intensity nonhuman primate novel object perception object recognition optical fiber public health relevance relating to nervous system research study spatiotemporal success tool visual stimulus

项目摘要

DESCRIPTION (provided by applicant): Visual object recognition is central to quality of life in health and disease, but it is not understood at a deep, mechanistic level. For example, while primate inferior temporal cortex (IT) is likely a key neuronal processing bottleneck, we still have only a dim understanding of its causal role at a fine spatial and temporal grain. This exploratory proposal (R21) aims to deploy, characterize, and behaviorally validate novel tools to produce spatially precise, temporally delimited silencing of neuronal activity in the IT cortex of the awak, behaving primate. Concretely, we want to choose a mm-scale location on a magnetic resonance image of a non-human primate brain, and then ask: what is the importance of normally-evoked neuronal activity at that location in supporting a given behavioral task? Rather than try to inject neuronal signals, our strategy is to develop methods to briefly (10-300 ms) block the neuronal activity that normally intervenes between visual stimulus onset and the animal's reaction time. To that end, this exploratory proposal has two synergistic aims: First, our preliminary results show that virally delivered optically-gated silencing molecules can indeed produce strong silencing of neuronal activity in IT cortex, but we have little understanding of the reliability, spatial extent and temporal limits of this silencing. Thus, we will (Aim 1) make x-ray targeted viral injections, followed by x-ray targeted optical fiber implantation, and spatially precise (~10 um) maps of neuronal silencing (or enhancement) effects in and around the optical fiber tip at multiple sites in IT cortex. The expected outcome is a spatiotemporal map of light-induced neuronal silencing around the optical fiber tip, and its dependence on light intensity, duration and latency. Second, we do not know if optical silencing of IT sub-regions leads to measurable behavioral effects on object recognition tasks. Thus, we have developed recognition tasks that are likely to be affected by IT silencing, and we have already discovered that pharmacological neuronal silencing at specific IT sub-regions (muscimol) leads to behavioral deficits in at least one recognition task (but not all such tasks). We now aim (Aim2) to test the ability of optical silencing tools to produce behavioral deficits in that same task at those same locations. The expected outcome is a demonstration that optical silencing of IT sub-regions can produce specific behavioral recognition deficits, as well as a comparison with pharmacologically induced deficits. If successful, the proposed work will enable entirely new lines of interventional work to systematically test the causal role of IT cortex in visual object recognition, and will contribute o a still nascent, but promising toolbox of optical techniques for systems-level questions in primates.

描述（由申请人提供）：视觉对象识别对于健康和疾病的生活质量至关重要，但人们对它的理解还不够深入、机械。例如，虽然灵长类动物的下颞叶皮层（IT）可能是一个关键的神经元处理瓶颈，但我们仍然有在精细的空间和时间粒度上对其因果作用只有模糊的理解。该探索性提案 (R21) 旨在部署、表征和行为验证新工具，以在清醒、行为灵长类动物的 IT 皮层中产生空间精确、时间限定的神经元活动沉默。具体来说，我们想要在非人类灵长类动物大脑的磁共振图像上选择一个毫米级的位置，然后问：该位置正常诱发的神经元活动在支持给定行为任务方面的重要性是什么？而不是尝试注入神经元信号，我们的策略是开发方法来短暂（10-300毫秒）阻断通常干预视觉刺激开始和动物反应时间之间的神经元活动。为此，这一探索性提议有两个协同目标：首先，我们的初步结果表明，病毒传递的光门控沉默分子确实可以对 IT 皮层的神经元活动产生强烈的沉默，但我们对其可靠性、空间范围和影响知之甚少。这种沉默的时间限制。因此，我们将（目标 1）进行 X 射线靶向病毒注射，然后进行 X 射线靶向光纤植入，并在光纤尖端内和周围绘制神经元沉默（或增强）效应的空间精确（~10 um）图IT 皮质的多个部位。预期结果是光纤尖端周围光诱导神经元沉默的时空图，及其对光强度、持续时间和延迟的依赖性。其次，我们不知道 IT 子区域的光学沉默是否会对对象识别任务产生可测量的行为影响。因此，我们开发了可能受到 IT 沉默影响的识别任务，并且我们已经发现特定 IT 子区域（蝇蕈醇）的药理神经元沉默会导致至少一项识别任务（但不是所有此类任务）的行为缺陷。任务）。我们现在的目标（目标2）测试光学沉默工具在相同位置的相同任务中产生行为缺陷的能力。预期结果是证明 IT 子区域的光学沉默可以产生特定的行为识别缺陷，并与药理学引起的缺陷进行比较。如果成功，拟议的工作将使全新的介入工作系列成为可能系统地测试 IT 皮层在视觉对象识别中的因果作用，并将为解决灵长类动物系统级问题提供一个仍处于新生阶段但很有前途的光学技术工具箱。