Cellular and circuit mechanisms mediating the cross-modal modulation of sensory processing

介导感觉处理跨模式调制的细胞和电路机制

• 批准号: 9906285
• 负责人: Benjamin Schuman
• 金额: $ 2.71万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906285
• 关键词: Acoustic Stimulation; Animals; Area; Auditory; Auditory area; Axon; Behavior; Brain; Cells; Dendrites; Electrophysiology (science); Environment; Goals; Head; Human; Ideal 1; Interneurons; Knowledge; Light; Mammals; Mediating; Mental disorders; Modality; Molecular; Morphology; Mus; Neocortex; Neurons; Output; Pattern; Perception; Pharmacology; Play; Positioning Attribute; Pyramidal Cells; Research; Role; Sensory; Signal Transduction; Slice; Somatosensory Cortex; Source; Stimulus; Structure; Study models; Synapses; Thalamic Nuclei; Thalamic structure; Touch sensation; Transgenic Mice; Vibrissae; Whole-Cell Recordings; Work; area striata; auditory stimulus; autism spectrum disorder; awake; experimental study; in vivo; multimodality; neocortical; neuronal cell body; neuroregulation; optogenetics; response; sensory cortex; sensory input; sensory integration; sound

Project Summary To perceive real-world objects and environments, animals must be able to combine sensory and contextual information. For mammals, the integration of sensory and contextual signals depends upon computations performed in the neocortex, a layered structure principally comprised of excitatory pyramidal cells and GABAergic inhibitory interneurons. Sensory processing in the neocortex is hierarchical and begins at primary sensory areas. Neocortical layer 4 receives input directly from the sensory thalamus, while layer 1 receives contextual input from a diversity of regions, including cortical areas processing different sensory modalities, higher-order thalamic nuclei, callosal input, neuromodulatory sources, and high-order cortical areas. Pyramidal cells, the main output cells of the neocortex, have two input zones: the basal dendrites, which eventually receive thalamic-driven sensory information, and the tuft dendrites, which project to layer 1. Neocortical layer 1 is unique among the cortical layers in that it exclusively contains GABAergic interneurons and no excitatory cells. Because they are positioned among the tuft dendrites of pyramidal cells and axonal projections carrying contextual information, the interneurons of L1 are ideal candidates to regulate the integration of sensory and contextual signals. Moreover, the functional importance of L1 interneurons in mediating the integration of contextual and sensory information has been demonstrated by recent studies. One such study has shown that L1 interneurons are critically important for the cross-modal adjustment of sensory signals in primary sensory cortices. However, the identity of interneurons in L1 is poorly understood, so their precise role in cross-modal neocortical circuits remains a mystery. My research has demonstrated that L1 contains four distinct subtypes of interneurons, each with a means of being targeted using transgenic mouse lines. With this knowledge, the purpose of this research is to discover cellular and circuit mechanisms that mediate cross-modal modulation of sensory processing in the neocortex. This goal will be achieved in two aims: (1) using optogenetics and electrophysiological recordings in brain slices, the subtypes of interneurons in L1 that receive cross-modal input and the roles those interneurons play in their local circuit will be determined; (2) using electrophysiological recordings in awake, head-fixed mice while manipulating the activity of interneurons in L1, the circuit mechanisms that regulate the cross-modal modulation of sensory processing will be determined. Results from these experiments will benefit our understanding of contextual processing in the neocortex and may shed light on the origins of deficits in sensory integration found in psychiatric disorders.

项目摘要 为了感知现实世界的物体和环境，动物必须能够将联合收割机的感觉和语境结合起来。 信息.对于哺乳动物来说，感觉和情境信号的整合依赖于计算 在新皮质中进行，新皮质是主要由兴奋性锥体细胞组成的分层结构， GABA能抑制性中间神经元。新皮层中的感觉处理是分层的， 感官区域新皮层第4层直接接收来自感觉丘脑的输入，而第1层接收来自感觉丘脑的输入。 来自不同区域的上下文输入，包括处理不同感觉模态的皮层区域， 高级丘脑核、胼胝体输入、神经调节源和高级皮质区。锥体 细胞，新皮层的主要输出细胞，有两个输入区：基底树突，最终 接收丘脑驱动的感觉信息，以及投射到第1层的簇状树突。新皮层第1层 在皮质层中是独特的，因为它只含有GABA能中间神经元，而没有兴奋性神经元。 细胞因为它们位于锥体细胞的簇状树突和轴突突起之间， 背景信息，L1的中间神经元是理想的候选人，以调节整合的感觉和 语境信号此外，L1中间神经元在介导整合的功能重要性， 最近的研究已经证明了上下文和感觉信息。其中一项研究表明， L1中间神经元对于初级感觉神经元中感觉信号的跨模态调节至关重要。 皮质然而，L1中中间神经元的身份知之甚少，因此它们在跨模态中的确切作用是不确定的。 新皮层回路仍然是个谜我的研究表明L1包含四种不同的亚型 中间神经元，每个中间神经元都有一种使用转基因小鼠系进行靶向的方法。有了这些知识， 本研究的目的是发现细胞和电路机制，介导的跨模态调制的 大脑皮层的感觉处理这一目标将通过两个目标来实现：（1）使用光遗传学， 脑切片的电生理记录，L1中接受交叉模态的中间神经元的亚型， 将确定输入和这些中间神经元在其局部回路中发挥的作用;（2）使用 电生理记录在清醒的，头部固定的小鼠，同时操纵活动的中间神经元在L1， 将确定调节感觉处理的交叉模态调制的电路机制。 这些实验的结果将有助于我们理解新皮层中的语境处理， 可能揭示在精神疾病中发现的感觉统合缺陷的起源。