Department of Bioengineering, University of Utah, Salt Lake City, UT 84112.
Department of Biomedical Engineering, Boston University, Boston, MA 02215.
eNeuro. 2017 Oct 16;4(5). doi: 10.1523/ENEURO.0263-16.2017. eCollection 2017 Sep-Oct.
Local GABAergic interneurons regulate the activity of spatially-modulated principal cells in the medial entorhinal cortex (MEC), mediating stellate-to-stellate connectivity and possibly enabling grid formation via recurrent inhibitory circuitry. Despite the important role interneurons seem to play in the MEC cortical circuit, the combination of low cell counts and functional diversity has made systematic electrophysiological studies of these neurons difficult. For these reasons, there remains a paucity of knowledge on the electrophysiological profiles of superficial MEC interneuron populations. Taking advantage of glutamic acid decarboxylase 2 (GAD2)-IRES-tdTomato and PV-tdTomato transgenic mice, we targeted GABAergic interneurons for whole-cell patch-clamp recordings and characterized their passive membrane features, basic input/output properties and action potential (AP) shape. These electrophysiologically characterized cells were then anatomically reconstructed, with emphasis on axonal projections and pial depth. K-means clustering of interneuron anatomical and electrophysiological data optimally classified a population of 106 interneurons into four distinct clusters. The first cluster is comprised of layer 2- and 3-projecting, slow-firing interneurons. The second cluster is comprised largely of PV+ fast-firing interneurons that project mainly to layers 2 and 3. The third cluster contains layer 1- and 2-projecting interneurons, and the fourth cluster is made up of layer 1-projecting horizontal interneurons. These results, among others, will provide greater understanding of the electrophysiological characteristics of MEC interneurons, help guide future in vivo studies, and may aid in uncovering the mechanism of grid field formation.
局部 GABA 能中间神经元调节内侧缰核皮质（MEC）中空间调制的主细胞的活动，介导星状细胞间的连接，并通过抑制性折返回路可能使栅格形成。尽管中间神经元在 MEC 皮质回路中似乎发挥了重要作用，但细胞数量少和功能多样性的结合使得对这些神经元进行系统的电生理研究变得困难。由于这些原因，关于浅层 MEC 中间神经元群体的电生理特征的知识仍然匮乏。利用谷氨酸脱羧酶 2（GAD2）-IRES-tdTomato 和 PV-tdTomato 转基因小鼠，我们针对 GABA 能中间神经元进行全细胞膜片钳记录，并对其被动膜特性、基本输入/输出特性和动作电位（AP）形状进行了特征描述。然后对这些电生理特征描述的细胞进行解剖重建，重点关注轴突投射和脑表面深度。对中间神经元解剖和电生理数据的 K-均值聚类将 106 个中间神经元最佳地分为四个不同的簇。第一簇由层 2 和 3 投射的慢放电中间神经元组成。第二簇主要由 PV+快速放电中间神经元组成，主要投射到 2 和 3 层。第三簇包含层 1 和 2 投射的中间神经元，第四簇由层 1 投射的水平中间神经元组成。这些结果，以及其他结果，将提供对 MEC 中间神经元电生理特征的更深入理解，有助于指导未来的体内研究，并可能有助于揭示栅格形成的机制。
