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.

视觉皮层状态依赖处理的细胞机制 目前对介导视觉信息和视觉感知处理的神经机制的理解很大程度上是 基于对麻醉或清醒且专注的大脑进行的实验结果。然而，这两种状态代表 连续警觉状态的两个极端，众所周知，人类和动物都会感知并做出反应 不专心、不警觉甚至浅睡时的刺激。事实上，最近对清醒小鼠和兔子的研究表明 警觉和非警觉状态之间的转换极大地改变了丘脑和皮质神经元的运作 视觉通路。然而，我们对突触输入、感受野和反应的变化了解有限。 不同类型的皮质神经元在多种状态下的特性，驱动这些状态的细胞机制 依赖性变化，以及这些状态依赖性变化如何影响视觉信息的皮层处理。致地址 我们的知识差距，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 安静地持续几个小时，并且表现出非常有限的眼球运动，同时自发地、自然地在警觉、 非警觉/困倦和睡眠状态。我们将从视觉皮层 (V1) 神经元和细胞外进行细胞内记录 在长期实验中，来自视网膜局部对齐区域的视觉丘脑（LGN）神经元的记录，同时 不吸毒的受试者在不同的大脑状态之间转换。我们将 (a) 识别不同类型的皮质投射神经元 和不同皮质层的中间神经元电生理学并使用逆向和顺向微刺激 不同的大脑结构； (b) 使用一系列视觉刺激来表征它们的感受野和响应特性； (c) 评估神经元反应中兴奋和抑制的贡献，并通过以下方式表征单单元计算 分析在对视觉刺激和注射的反应过程中阈下活动向尖峰序列的转化 波动电流； (d) 使用其特征信号严格量化每个大脑状态和它们之间的转换 在海马体和新皮质记录的脑电图中。这些实验将提供关于丘脑如何输入的独特数据， 不同类型的皮质神经元的视觉反应和感受野在广泛的大脑状态下发生变化，并且 研究这种状态依赖性的机制，包括突触输入的变化、单单元计算和 激发/抑制平衡。拟议研究的结果将有助于进一步理解如何 大脑状态影响视觉处理和视觉感知。 据美国国家公路交通安全管理局称，已有超过 1,550 人死亡，超过 71,000 人被救。 每年都有因注意力下降和困倦引起的事故受伤。拟议的工作将带来更好的结果 了解视觉处理的状态依赖性，并将为进一步研究和开发工具提供信息 检测注意力下降并预防“疲劳驾驶”事故。它还将为进一步的研究提供信息 与注意力受损和/或机制功能障碍引起的知觉缺陷相关的认知障碍 调节唤醒-睡眠周期。