Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.
J Physiol. 2011 Jun 1;589(Pt 11):2767-79. doi: 10.1113/jphysiol.2011.208637. Epub 2011 Apr 11.
Hypothalamic hypocretin/orexin (Hcrt/Orx) neurons recently emerged as critical regulators of sleep–wake cycles, reward seeking and body energy balance. However, at the level of cellular and network properties, it remains unclear whether Hcrt/Orx neurons are one homogeneous population, or whether there are several distinct types of Hcrt/Orx cells. Here, we collated diverse structural and functional information about individual Hcrt/Orx neurons in mouse brain slices, by combining patch-clamp analysis of spike firing, membrane currents and synaptic inputs with confocal imaging of cell shape and subsequent 3-dimensional Sholl analysis of dendritic architecture. Statistical cluster analysis of intrinsic firing properties revealed that Hcrt/Orx neurons fall into two distinct types. These two cell types also differ in the complexity of their dendritic arbour, the strength of AMPA and GABAA receptor-mediated synaptic drive that they receive, and the density of low-threshold, 4-aminopyridine-sensitive, transient K+ current. Our results provide quantitative evidence that, at the cellular level, the mouse Hcrt/Orx system is composed of two classes of neurons with different firing properties, morphologies and synaptic input organization.
下丘脑食欲素/孤啡肽（Hcrt/Orx）神经元最近被认为是睡眠-觉醒周期、奖励寻求和身体能量平衡的关键调节因子。然而，在细胞和网络特性水平上，尚不清楚 Hcrt/Orx 神经元是一个均质群体，还是存在几种不同类型的 Hcrt/Orx 细胞。在这里，我们通过结合对 Spike 放电、膜电流和突触输入的膜片钳分析以及对细胞形状的共聚焦成像以及随后的 3 维 Sholl 分析树突结构，对小鼠脑片中单一 Hcrt/Orx 神经元的多种结构和功能信息进行了整理。对固有放电特性的统计聚类分析表明，Hcrt/Orx 神经元分为两种不同类型。这两种细胞类型在树突结构的复杂性、它们所接收的 AMPA 和 GABAA 受体介导的突触驱动的强度以及低阈值、4-氨基吡啶敏感、瞬态 K+电流的密度方面也存在差异。我们的结果提供了定量证据，表明在细胞水平上，小鼠 Hcrt/Orx 系统由具有不同放电特性、形态和突触输入组织的两类神经元组成。
