INTERNEURONS MEDIATING FEEDFORWARD THALAMOCORTICAL INHIBITION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。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得更紧密；因此，了解大脑皮层的工作原理是理解我们作为个体和物种的先决条件，具有巨大的临床重要性。大脑皮层通过丘脑接收来自听觉、视觉和躯体感觉模式的大部分传入感觉信息，并最终负责将这些感觉输入转换为我们称为知觉的意识体验。因此，确定丘脑皮质网络的基本成分并阐明它们的突触联系是理解导致感觉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棘状星状细胞，即以谷氨酸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起前馈抑制，限制其在时间和空间上的放电，并提高代表感觉事件的时空皮质激活模式的信噪比。大约三分之二的皮质抑制神经元属于两个不重叠的神经化学群：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“快脉冲”神经元，被认为主要在躯体和近端的树突上突触，而含有生长抑素的中间神经元通常是“低阈值的尖峰”神经元，似乎更喜欢远端的树突靶点。这些在固有特性和突触靶向性上的显著差异有力地表明，这两个亚类在丘脑皮质计算中可能扮演着相当不同的角色，涉及到感觉加工。这项研究的目的是通过比较这两种神经元亚型引起的前馈抑制的电生理特性和潜在的结构基础来检验这一假说，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中所扮演的不同角色。

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.