INTERNEURONS MEDIATING FEEDFORWARD THALAMOCORTICAL INHIBITION

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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联系更紧密;因此，了解大脑皮层的工作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、视觉和躯体感觉的大部分感官信息，并最终负责将这些感官输入转化为我们称之为感知的意识体验。因此，识别丘脑皮层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觉知觉的皮层计算的先决条件。 大约75-80%的皮质神经元是锥体或棘状星状细胞，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。丘脑受体层（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，从而在其靶神经元中引发前馈抑制，该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质激活模式的信噪比。大约三分之二的皮层抑制性神经元属于两个不重叠的神经化学群：含小白蛋白的中间神经元和含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，并且被认为主要在胞体和近端树突上突触，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靶。这些显着的差异，内在的属性和突触靶向强烈表明，这两个子类可能发挥相当不同的作用，在丘脑皮质计算涉及的感觉处理。该研究的目的是通过比较这两种interneuronal亚型引起的前馈抑制的电生理特性和潜在的结构基础来验证这一假设，从而首次阐明GABA能interneurons的特定亚类在皮层处理感觉相关输入时所起的不同作用。

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.