Supplement to Communication between Networks: Context, Inhibition, and Neuromodulation

网络间通信的补充：情境、抑制和神经调节

• 批准号: 10478350
• 负责人: Caroline Anne Runyan
• 金额: $ 16.6万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10478350
• 关键词: Affect; Animals; Area; Attention; Auditory; Behavioral; Brain; Brain Diseases; Brain region; Calcium; Cerebral cortex; Communication; Complex; Disease; Dissection; Foundations; Future; Goals; Head; Image; Label; Monitor; Mus; Perception; Performance; Process; Role; Running; Schizophrenia; Sensory; Signal Transduction; Societies; Source; Stimulus; Stream; System; addiction; auditory stimulus; autism spectrum disorder; behavioral response; cell type; cognitive process; excitatory neuron; experimental study; flexibility; information processing; inhibitory neuron; neuroregulation; operation; optogenetics; recruit; relating to nervous system; response; sensory stimulus; signal processing; tool; transmission process; treadmill; two-photon; virtual reality; visual stimulus

Project Summary The brain is often bombarded by streams of information from multiple sources simultaneously. In real world situations, rapidly changing contexts can shift the meaning of a sensory stimulus, requiring an animal to change its response to a given stimulus on the fly. The ability to flexibly and appropriately adjust behavioral responses in changing contexts is critical not only for survival, but also to thrive in society. Indeed, disruptions in this ability characterize many brain disorders. The goal of our lab is to understand the mechanisms that underlie the flexibility of information processing in cortical circuits, focusing on how inhibitory neurons gate the flow of information between sensory and association regions in a context-dependent manner. Head-fixed mice voluntarily running on a spherical treadmill will be rapidly shifted between behavioral contexts within single sessions. These contexts will include spontaneous (no experimenter-controlled sensory stimulation), passive delivery of visual and auditory stimuli, and active performance of auditory perceptual tasks in virtual reality. In each of these contexts, two-photon imaging of calcium activity will be used to monitor the responses of hundreds of genetically labeled inhibitory and excitatory neurons simultaneously. In some experiments, optogenetics will be used to activate specific incoming projections to the imaged region, or to inactivate specific cell types. These tools will be combined in three main projects. In the first project, the inhibitory mechanisms gating the flow of information between cortical regions will be dissected, to determine whether canonical rules define inhibitory operations across cortex, or if local specializations allow greater flexibility at different hierarchical levels of the cerebral cortex. In the second project, the roles of inhibitory neurons in setting network dynamics will be determined, and the consequences of shifting network dynamics on signal processing will be defined. In the third project, neuromodulatory recruitment of inhibitory circuits across the cortical hierarchy will be described, to determine how shifts in brain state affect information processing. To understand the neural underpinnings of perception, attention, and behavioral flexibility, it is critical to study the interaction between brain areas, rather than to focus on single brain regions in isolation. The experiments proposed here will use new tools to answer fundamental questions about how local circuits interact to process information, toward the goal of understanding how the distributed cortical network gives rise to cognitive processes such as attention and perception.

项目摘要 大脑通常会同时受到来自多个来源的信息流的轰炸。在现实世界中 情况，快速变化的环境可以改变感官刺激的含义，要求动物 改变其对给定刺激的反应。灵活和适当调整行为的能力 在不断变化的环境中的反应不仅对生存至关重要，而且对于在社会中蓬勃发展至关重要。确实，破坏了 以这种能力为特征，许多脑部疾病。我们实验室的目的是了解 基于皮质电路中信息处理的灵活性，重点是抑制神经元如何 感官和关联区域之间的信息流以上下文依赖性方式。头部固定小鼠 在球形跑步机上自愿奔跑将在单个行为环境之间迅速转移 会议。这些环境将包括自发的（无实验者控制的感觉刺激），被动 交付视觉和听觉刺激，以及在虚拟现实中的听觉感知任务的积极性能。在 这些上下文中的每一个，钙活性的两光子成像将用于监视 数百个遗传标记的抑制性和兴奋性神经元同时标记。在某些实验中 光遗传学将用于激活对成像区域的特定传入投影，或灭活特定 细胞类型。这些工具将组合在三个主要项目中。在第一个项目中，抑制机制 将剖析皮质区域之间的信息流，以确定是否规范规则 定义跨皮质的抑制作用，或者如果局部专业化允许在不同 大脑皮层的分层水平。在第二个项目中，抑制神经元在设置中的作用 将确定网络动力学，以及在信号上转移网络动态的后果 处理将定义。在第三个项目中，神经调节性的抑制回路招募 将描述皮质层次结构，以确定大脑状态的变化如何影响信息处理。到 了解感知，注意力和行为灵活性的神经基础，研究 大脑区域之间的相互作用，而不是孤立地关注单个大脑区域。实验 这里提出的将使用新工具来回答有关本地电路如何相互作用的基本问题 信息，目的是了解分布式皮质网络如何产生认知 注意和感知等过程。