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

• 批准号: 8427417
• 负责人: James J DiCarlo
• 金额: $ 21.16万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 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/8427417
• 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

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）：视觉物体识别对健康和疾病的生活质量至关重要，但它在深层次的机械层面上还没有被理解。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