Dichotomous Cellular Properties of Mouse orexin/hypocretin Neurons

J Physiol. 2011 Jun 1;589(Pt 11):2767-79. doi: 10.1113/jphysiol.2011.208637. Epub 2011 Apr 11.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Action Potentials / physiology
  • Animals
  • Brain / cytology*
  • Cell Shape / physiology
  • Cluster Analysis
  • Dendrites / physiology
  • Electrophysiological Phenomena / physiology*
  • Excitatory Postsynaptic Potentials / physiology
  • GABA-A Receptor Antagonists / pharmacology
  • Green Fluorescent Proteins / genetics
  • Inhibitory Postsynaptic Potentials / physiology
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mice, Transgenic
  • Miniature Postsynaptic Potentials / physiology
  • Neurons / cytology*
  • Neurons / physiology*
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Orexins
  • Patch-Clamp Techniques
  • Potassium Channels, Voltage-Gated / antagonists & inhibitors
  • Potassium Channels, Voltage-Gated / metabolism
  • Promoter Regions, Genetic / genetics
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, AMPA / metabolism
  • Receptors, GABA-A / metabolism

Substances

  • GABA-A Receptor Antagonists
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Potassium Channels, Voltage-Gated
  • Receptors, AMPA
  • Receptors, GABA-A
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • 4-Aminopyridine