Dichotomous cellular properties of mouse orexin/hypocretin neurons

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 GABA_A 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.