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The Role of Dendrites in Thalamocortical Circuitry

树突在丘脑皮质回路中的作用

基本信息

批准号：
8640986
负责人：
Randy M Bruno
金额：
$ 34.03万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8640986
关键词：
Action Potentials Address Affect Attenuated Axon Biological Assay Biological Neural Networks Brain region Cell membrane Cells Communication Complex Confocal Microscopy Dendrites Disease Distal Electron Microscopy Exhibits Generations Genetic Goals Individual Label Lead Location Maps Measures Mediating Membrane Membrane Potentials Methods Modeling N-Methyl-D-Aspartate Receptors N-Methylaspartate National Institute of Neurological Disorders and Stroke Neocortex Nervous system structure Neurodegenerative Disorders Neurons Process Property Relative (related person)Role Seizures Sensory Sensory Process Signal Transduction Staging Strategic Planning Sum Synapses Synaptic Potentials Testing Thalamic structure Time Trees Tremor Vertebral column Whole-Cell Recordings attenuation extracellular hippocampal pyramidal neuron in vivo millisecond nervous system disorder neurological pathology neuronal cell body public health relevance receptive field research study response sensory cortex sensory stimulus simulation voltage voltage gated channel

项目摘要

DESCRIPTION (provided by applicant): Many diseases of the nervous system are now thought to involve breakdowns in communication among neurons within and between brain regions. The conventional model for the flow of activity in neural networks is that synaptic inputs from neurons at one stage of processing are summed by any given neuron in the next stage. In reality though, synapses are made onto long, branching dendritic trees that can have complicated effects on normal integration of synaptic inputs. First, the dendritic membrane itself attenuates any synaptically-evoked electrical signal being conducted along the tree to the cell body. Diminished signals may be less likely to contribute to a neuronal discharge and to activate downstream synapses onto other neurons. Second, the coincident activation of several neighboring synapses can open specialized voltage-gated channels in the cell membrane, generating a dendritic "spike" in membrane potential larger than the sum of the individual synaptic signals. The aims of this project are to understand how each of these two dendritic properties affect cortical activity and processing of sensory stimuli, with a focus on the initial stages of processing in neocortex. Processing is thought to begin with sensory information from the outside world entering sensory cortex via thalamocortical synapses from thalamus to cortical layer 4. Thalamocortical synapses are thought to be individually stronger than corticocortical synapses. The first aim is to test whether thalamocortical synapses onto a cortical dendritic tree are closer to the cell body, a potential mechanism for the greater relative efficacy of thalamocortical connections. Correlative confocal and electron microscopy will be used to map the locations of synapses across the dendritic trees of cortical neurons. Receptive fields of labeled pairs of individual thalamic and cortical neurons will be measured to ask if dendritic attenuation contributes to how cortical neurons are tuned to particular sensory stimuli. The second aim is to ask if dendritic spikes boost the ability of thalamocortical synapses to directly activate cortical neurons. This will be tested by combining intracellular recording in vivo with pharmacological blockade of voltage-gated channels or individual cortical layers. Confocal microscopy will additionally be used to test whether thalamocortical synapses are sufficiently clustered along cortical dendrites to engage dendritic spikes. If these aims show that synaptic location is important, subtle mistargeting of synapses by dysfunctional genetic or activity-dependent mechanisms would lead to abnormal flow of excitation between brain regions, potentially initiating or contributing to seizure- or tremor-like activity in neurological diseases.

描述（由申请人提供）：现在认为许多神经系统疾病与大脑区域内部和之间的神经元之间的通讯中断有关。神经网络中活动流的传统模型是，处理一个阶段的神经元的突触输入由下一阶段的任何给定神经元求和。但实际上，突触是长长的、有分支的树突树，这可能会对突触输入的正常整合产生复杂的影响。首先，树突膜本身会减弱沿着树传导到细胞体的任何突触诱发的电信号。信号减弱可能不太可能导致神经元放电并激活其他神经元的下游突触。其次，几个相邻突触的同时激活可以打开细胞膜中专门的电压门控通道，产生大于单个突触信号总和的膜电位树突“尖峰”。该项目的目的是了解这两种树突特性如何影响皮质活动和感觉刺激的处理，重点关注新皮质处理的初始阶段。人们认为，处理过程始于来自外界的感觉信息通过从丘脑到皮质层 4 的丘脑皮质突触进入感觉皮层。丘脑皮质突触被认为比皮质皮质突触个体更强。第一个目的是测试皮质树突树上的丘脑皮质突触是否更接近细胞体，这是丘脑皮质连接相对功效更大的潜在机制。相关共焦和电子显微镜将用于绘制皮质神经元树突树上突触的位置。将测量标记对的单个丘脑和皮质神经元的感受野，以询问树突衰减是否有助于皮质神经元如何适应特定的感觉刺激。第二个目的是询问树突尖峰是否增强丘脑皮层突触直接激活皮层神经元的能力。这将通过将体内细胞内记录与电压门控通道或单个皮质层的药理学阻断相结合来进行测试。共聚焦显微镜还将用于测试丘脑皮质突触是否沿着皮质树突充分聚集以接合树突尖峰。如果这些目标表明突触位置很重要，那么功能失调的遗传或活动依赖性机制对突触的微妙定位将导致大脑区域之间的异常兴奋流动，可能引发或促成神经系统疾病中的癫痫或震颤样活动。