Cellular Mechanisms of State-Dependent Processing in Visual Cortex

视觉皮层状态相关处理的细胞机制

• 批准号: 10736387
• 负责人: Yulia Bereshpolova
• 金额: $ 40.25万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736387
• 关键词: Accidents; Action Potentials; Address; Affect; Anesthesia procedures; Animal Experiments; Animals; Attention; Brain; Cells; Characteristics; Chronic; Cognition Disorders; Contrast Sensitivity; Data; Dependence; Detection; Drowsiness; Drowsy Driving; Electric Stimulation; Electroencephalography; Electrophysiology (science); Equilibrium; Evoked Potentials; Exhibits; Eye Movements; Felis catus; Frequencies; Functional disorder; Goals; Hippocampus; Hour; Human; Impairment; Individual; Injections; Interneurons; Knowledge; Lateral Geniculate Body; Light; Location; Measures; Mediating; Membrane Potentials; Monkeys; Mus; Neocortex; Neurons; Noise; Oryctolagus cuniculus; Pattern; Perception; Persons; Pharmaceutical Preparations; Photic Stimulation; Physiologic pulse; Prevention; Property; Pupil; REM Sleep; Regulation; Research; Rest; Safety; Site; Sleep; Sleep Wake Cycle; Slow-Wave Sleep; Stimulus; Structure; Synapses; Testing; Thalamic structure; Training; V1 neuron; Vision; Visual; Visual Cortex; Visual Pathways; Visual Perception; Visual System; Visual evoked cortical potential; Work; alertness; awake; cell type; corticogeniculate; differential expression; electrical microstimulation; experimental study; extracellular; information processing; injured; microstimulation; neocortical; operation; postsynaptic; prevent; receptive field; research and development; response; retinotopic; sensory input; sleep spindle; tool development; visual information; visual processing; visual stimulus; voltage

Cellular mechanisms of state-dependent processing in visual cortex Current understanding of neuronal mechanisms mediating processing of visual information and visual perception is largely based on results from experiments on either anesthetized or awake and attentive brains. However, these two states represent two extremes on a continuum of states of alertness, and it is known that both humans and animals perceive and respond to stimuli when non-attentive, nonalert and even during light sleep. Indeed, recent studies in awake mice and rabbits revealed that transitions between alert and nonalert states dramatically change the operation of thalamic and cortical neurons along the visual pathway. However, we have a limited knowledge of changes of synaptic inputs, receptive fields and response properties of different types of cortical neurons over a broad range of states, the cellular mechanisms that drive these state- dependent changes, and how these state-dependent changes affect cortical processing of visual information. To address these gaps in our knowledge, we will exploit advantages of the visual system of rabbit, an experimental animal that can sit quietly for hours and exhibits very limited eye movements while spontaneously and naturally transitioning between alert, nonalert/drowsy and sleep states. We will make intracellular recordings from visual cortex (V1) neurons and extracellular recordings from neurons in the visual thalamus (LGN) in retinotopically aligned regions, in chronic experiments, while drug-free subjects transition between different brain states. We will (a) identify different types of cortical projection neurons and interneurons in different cortical layers electrophysiologically and using antidromic and ortodromic microstimulation in different brain structures; (b) characterize their receptive fields and response properties using a battery of visual stimuli; (c) assess the contribution of excitation and inhibition in neuronal responses, and characterize single-unit computations by analyzing the transformation of subthreshold activity into spike trains during responses to visual stimuli and injection of fluctuating currents; (d) rigorously quantify each brain state and transition between them using their characteristic signatures in the EEG recorded in the hippocampus and neocortex. These experiments will provide unique data on how thalamic inputs, visual responses and receptive fields in cortical neurons of different types change over a broad range of brain states, and investigate mechanisms of this state-dependence in terms of changes of synaptic inputs, single-unit computations, and excitation/inhibition balance. Results of the proposed research will help to achieve the next level of understanding of how brain state affects visual processing and visual perception. According to the National Highway Traffic Safety Administration, more than 1,550 people are killed and over 71,000 are injured each year in accidents caused by decreased attention and drowsiness. The proposed work will lead to a better understanding of state-dependence of visual processing and will inform further research and development of tools for detection of decreased attention and prevention of "drowsy driving" accidents. It will also inform further research into cognitive disorders associated with deficits in perception caused by impaired attention and/or dysfunction of mechanisms regulating wake-sleep cycle.

视觉皮层中状态依赖性加工的细胞机制 当前对介导视觉信息和视觉感知处理的神经元机制的理解在很大程度上是 基于关于麻醉或清醒和细心的大脑实验的结果。但是，这两个状态代表 在机敏状态的连续体上有两个极端，众所周知，人类和动物都对 刺激当非竞争时，非电脑甚至在轻度睡眠期间。确实，最近对清醒小鼠和兔子的研究揭示了 这在警报和非校长状态之间的过渡会极大地改变丘脑和皮质神经元的操作 视觉途径。但是，我们对突触输入，接受场和反应的变化的了解有限 不同类型的皮质神经元的性质在广泛的状态下，驱动这些状态的细胞机制 依赖性变化以及这些依赖性变化如何影响视觉信息的皮质处理。解决 这些差距在我们的知识上，我们将利用兔子视觉系统的优势，兔子是一种可以坐的实验动物 静静地持续数小时，并且眼睛动作非常有限，同时自然而自然地在警报之间过渡， 非攻击/昏昏欲睡和睡眠状态。我们将从视觉皮层（V1）神经元和细胞外进行细胞内记录 在视网膜上对齐区域中的视觉丘脑（LGN）中的神经元的录音，慢性实验，而 不同大脑状态之间的无药物受试者过渡。我们将（a）识别不同类型的皮质投影神经元 以及不同皮质层中的中间神经元在电生理学上以及使用抗体和性质细胞微刺激 在不同的大脑结构中； （b）使用一系列视觉刺激来表征他们的接受场和响应特性； （c）评估神经元反应中激发和抑制作用的贡献，并通过通过单位计算来表征 在对视觉刺激的响应和注入时，分析亚阈值活动向尖峰火车的转化 波动的电流； （d）严格量化每个大脑状态并使用其特征签名之间的过渡 在海马和新皮层中记录的脑电图中。这些实验将提供有关丘脑输入方式的独特数据， 不同类型的皮质神经元中的视觉反应和接受场在广泛的大脑状态下变化，并且 根据突触输入，单单元计算和 激发/抑制平衡。拟议的研究的结果将有助于实现对如何 大脑状态会影响视觉处理和视觉感知。 根据国家公路交通安全管理局的数据，超过1,550人被杀，超过71,000人 每年因注意力减少和嗜睡而导致的事故受伤。拟议的工作将导致更好 了解视觉处理的状态依赖性，并将为工具的进一步研究和开发提供信息 检测注意力减少和预防“昏昏欲睡”事故。它还将为您提供进一步的研究 与机制的注意力和/或功能障碍引起的感知缺陷相关的认知障碍 调节尾流循环。