INTERNEURONS MEDIATING FEEDFORWARD THALAMOCORTICAL INHIBITION

中间神经元介导前向丘脑皮质抑制

• 批准号: 7609752
• 负责人: ARIEL AGMON
• 金额: $ 25.3万
• 依托单位: WEST VIRGINIA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7609752
• 关键词: Auditory; Brain region; Cerebral cortex; Chromosome Pairing; Clinical; Computer Retrieval of Information on Scientific Projects Database; Conscious; Dendrites; Distal; Employee Strikes; Event; Fire - disasters; Funding; Glutamates; Goals; Grant; Human; Individual; Institution; Interneurons; Link; Mediating; Modality; Neurons; Neurotransmitters; Noise; Parvalbumins; Pattern; Perception; Play; Property; Research; Research Personnel; Resources; Rest; Role; Role playing therapy; Sensory; Sensory Process; Signal Transduction; Somatostatin; Source; Synapses; Testing; Thalamic structure; Thinking; Time; United States National Institutes of Health; Visual; Work; base; excitatory neuron; experience; inhibitory neuron; neurochemistry; neuronal cell body; somatosensory; spatiotemporal; stellate cell

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Of all human brain regions, none is more closely linked with our uniquely human qualities than the cerebral cortex; understanding the workings of the cerebral cortex is therefore a prerequisite for understanding ourselves as individuals and as a species, and is of immense clinical importance. The cerebral cortex receives, via the thalamus, the majority of incoming sensory information from the auditory, visual and somatosensory modalities, and is ultimately responsible for transforming these sensory inputs into the conscious experience we call perception. Identifying the fundamental components of the thalamocortical network and elucidating their synaptic connections is therefore a prerequisite for understanding the cortical computations leading to sensory perception. About 75-80% of all cortical neurons are either pyramidal or spiny stellate cells, excitatory neurons using glutamate as a neurotransmitter; the rest are GABAergic inhibitory interneurons. GABAergic interneurons within the thalamo-recipient layers (layer 4 and the layers 5/6 junction) are strongly excited by thalamocortical inputs, thereby eliciting in their target neurons feedforward inhibition that constrains their firing in time and space, and enhances the signal-to-noise ratio of the spatiotemporal cortical activation patterns representing the sensory event. About two-thirds of all cortical inhibitory neurons belong to two non-overlapping neurochemical groups: parvalbumin-containing interneurons and somatostatin-containing interneurons. Parvalbumin-containing interneurons are "fast spiking" neurons, and are thought to synapse mostly on somata and proximal dendrites, while somatostatin-containing interneurons are often "low-threshold spiking" neurons, and seem to prefer distal dendritic targets. These striking differences in intrinsic properties and synaptic targeting strongly suggest that these two subclasses may play quite distinct roles in thalamocortical computations involved is sensory processing. The goal of the proposed study is to test this hypothesis by comparing the electrophysiological properties and the underlying structural basis of feedforward inhibition elicited by these two interneuronal subtypes, and thus for the first time illuminate the differential roles played by specific subclasses of GABAergic interneurons during cortical processing of sensory-related inputs.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 在人类所有的大脑区域中，没有一个区域比大脑皮层与我们独特的人类品质的联系更紧密。因此，了解大脑皮层的工作原理是了解我们作为个体和物种的先决条件，并且具有巨大的临床重要性。大脑皮层通过丘脑接收来自听觉、视觉和体感方式的大部分传入感觉信息，并最终负责将这些感觉输入转化为我们称为感知的意识体验。因此，识别丘脑皮质网络的基本组成部分并阐明它们的突触连接是理解导致感官知觉的皮质计算的先决条件。 大约 75-80% 的皮质神经元是锥体或刺星状细胞，即使用谷氨酸作为神经递质的兴奋性神经元；其余的是 GABA 能抑制性中间神经元。丘脑接受层（第 4 层和第 5/6 层交界处）内的 GABA 能中间神经元受到丘脑皮质输入的强烈兴奋，从而在其目标神经元中引发前馈抑制，限制其在时间和空间上的放电，并增强代表感觉事件的时空皮层激活模式的信噪比。大约三分之二的皮质抑制性神经元属于两个不重叠的神经化学组：含有小白蛋白的中间神经元和含有生长抑素的中间神经元。含有小白蛋白的中间神经元是“快速尖峰”神经元，并且被认为主要在体细胞和近端树突上突触，而含有生长抑素的中间神经元通常是“低阈值尖峰”神经元，并且似乎更喜欢远端树突目标。这些内在特性和突触靶向的显着差异强烈表明，这两个子类可能在涉及感觉处理的丘脑皮层计算中发挥着截然不同的作用。本研究的目的是通过比较这两种中间神经元亚型引起的前馈抑制的电生理学特性和潜在结构基础来检验这一假设，从而首次阐明 GABA 能中间神经元的特定亚类在感觉相关输入的皮层处理过程中所发挥的差异作用。