Convergent inputs from electrically and topographically distinct orexin cells to locus coeruleus and ventral tegmental area

J Antonio González, Lise T Jensen, Lars Fugger, Denis Burdakov

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46 Citations (Scopus)


Orexin/hypocretin (orx/hcrt) neurons are thought to ensure that reward-seeking is accompanied by alertness, but the underlying circuit organization is unclear. Reports of differential regulation of lateral versus medial orx/hcrt cells produced a hypothesis of 'efferent dichotomy', in which lateral orx/hcrt cells innervate the ventral tegmental area (VTA) and control reward, while medial orx/hcrt cells innervate locus coeruleus (LC) and control arousal. Two distinct types of orx/hcrt cells also emerged from analysis of intrinsic and input-driven single-cell electrical activity. To examine the projections of these emerging orx/hcrt subtypes to LC and VTA, we injected retrograde tracer into these regions in the mouse brain in vivo, and then examined the properties of tracer-containing orx/hcrt cells in hypothalamic slices. VTA- and LC-projecting orx/hcrt cells were found across the entire orx/hcrt field, including the zona incerta, perifornical area, dorsomedial/anterior and lateral hypothalamus. Within these areas, orx/hcrt cells had similar probabilities of projecting to VTA or LC. Examination of lateral versus medial sections revealed that VTA and LC received inputs from both lateral and medial orx/hcrt cells, but, unexpectedly, lateral orx/hcrt cells were more likely to project to LC than medial orx/hcrt cells. Finally, patch-clamp recordings revealed that VTA and LC received projections from both electrical classes of orx/hcrt cells, which had similar likelihoods of projecting to VTA or LC. Contrary to previous predictions, our data suggest that medial and lateral orx/hcrt cells, and the different electrical and morphological subclasses of orx/hcrt cells identified to date, send projections to both LC and VTA.

Original languageEnglish
Pages (from-to)1426-1432
Number of pages7
JournalEuropean Journal of Neuroscience
Issue number9
Early online date16 Apr 2012
Publication statusPublished - May 2012

Bibliographical note

This work was funded by the European Research Council (FP7)


  • Animals
  • Brain Mapping
  • Cell Count
  • Green Fluorescent Proteins
  • Hypothalamus
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials
  • Intracellular Signaling Peptides and Proteins
  • Locus Coeruleus
  • Mice
  • Mice, Transgenic
  • Microscopy, Confocal
  • Microspheres
  • Neural Pathways
  • Neurons
  • Neuropeptides
  • Orexins
  • Rhodamines
  • Ventral Tegmental Area
  • Journal Article
  • Research Support, Non-U.S. Gov't


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