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 大脑经常同时受到来自多个来源的信息流的轰炸。在真实的世界里 在某些情况下，快速变化的环境可以改变感官刺激的意义，这需要动物 改变它对给定刺激的反应。灵活和适当地调整行为的能力 在不断变化的环境中采取应对措施不仅对生存至关重要，而且对社会繁荣也至关重要。事实上，中断 这种能力是许多大脑疾病的特征。我们实验室的目标是了解 在皮层回路中信息处理的灵活性的基础，重点是抑制性神经元如何门控 信息在感觉区域和关联区域之间以依赖于上下文的方式流动。头部固定小鼠 自愿在球形跑步机上跑步将在单一的行为环境之间迅速转换。 sessions.这些情境将包括自发的（没有实验者控制的感觉刺激）、被动的（没有实验者控制的感觉刺激）和被动的（没有实验者控制的感觉刺激）。 视觉和听觉刺激的传递，以及虚拟现实中听觉感知任务的主动表现。在 在每一种情况下，钙活性的双光子成像将用于监测 数百个基因标记的抑制性和兴奋性神经元。在一些实验中， 光遗传学将被用于激活特定的传入投射到成像区域，或激活特定的 细胞类型。这些工具将合并为三个主要项目。在第一个项目中， 将对皮层区域之间的信息流进行门控分析，以确定规范规则是否 定义跨皮层的抑制性操作，或者如果局部特化允许在不同的 大脑皮层的等级结构在第二个项目中，抑制性神经元在设置中的作用 将确定网络动态，以及改变网络动态对信号的影响。 处理将被定义。在第三个项目中，神经调节性募集抑制回路跨越 将描述皮层层次结构，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，研究这些神经基础是至关重要的。 这是一个很好的方法，可以帮助我们了解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的工具来回答关于局部电路如何相互作用以处理 信息，朝着理解分布式皮层网络如何引起认知的目标， 注意力和知觉等过程。