Laboratory of Molecular Neurobiology, Department Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden.
Section on Cellular and Synaptic Physiology, Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA.
Sci Rep. 2020 Sep 24;10(1):15680. doi: 10.1038/s41598-020-72588-1.
Determining the cellular content of the nervous system in terms of cell types and the rules of their connectivity represents a fundamental challenge to the neurosciences. The recent advent of high-throughput techniques, such as single-cell RNA-sequencing has allowed for greater resolution in the identification of cell types and/or states. Although most of the current neuronal classification schemes comprise discrete clusters, several recent studies have suggested that, perhaps especially, within the striatum, neuronal populations exist in continua, with regards to both their molecular and electrophysiological properties. Whether these continua are stable properties, established during development, or if they reflect acute differences in activity-dependent regulation of critical genes is currently unknown. We set out to determine whether gradient-like molecular differences in the recently described Pthlh-expressing inhibitory interneuron population, which contains the Pvalb-expressing cells, correlate with differences in morphological and connectivity properties. We show that morphology and long-range inputs correlate with a spatially organized molecular and electrophysiological gradient of Pthlh-interneurons, suggesting that the processing of different types of information (by distinct anatomical striatal regions) has different computational requirements.
确定神经系统的细胞内容,包括细胞类型和它们的连接规则,是神经科学的一个基本挑战。高通量技术(如单细胞 RNA 测序)的出现,使得在鉴定细胞类型和/或状态方面具有更高的分辨率。尽管大多数现有的神经元分类方案包括离散的簇,但最近的几项研究表明,特别是在纹状体中,神经元群体在分子和电生理特性方面存在连续性。这些连续性是稳定的特性,是在发育过程中建立的,还是反映了关键基因的活性依赖性调节的急性差异,目前尚不清楚。我们着手确定最近描述的 Pthlh 表达抑制性中间神经元群体(包含 Pvalb 表达细胞)中是否存在类似梯度的分子差异与形态和连接性特征的差异相关。我们表明,形态和长程输入与 Pthlh 中间神经元的空间组织分子和电生理梯度相关,这表明不同类型的信息(通过不同的解剖纹状体区域)的处理具有不同的计算要求。