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

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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
Volume35
Issue number9
Early online date16 Apr 2012
DOIs
Publication statusPublished - May 2012

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Ventral Tegmental Area
Locus Coeruleus
Orexins
Reward
Lateral Hypothalamic Area
Anterior Hypothalamus
Internal-External Control
Arousal

Keywords

  • 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

Cite this

Convergent inputs from electrically and topographically distinct orexin cells to locus coeruleus and ventral tegmental area. / González, J Antonio; Jensen, Lise T; Fugger, Lars; Burdakov, Denis.

In: European Journal of Neuroscience, Vol. 35, No. 9, 05.2012, p. 1426-1432.

Research output: Contribution to journalArticle

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T1 - Convergent inputs from electrically and topographically distinct orexin cells to locus coeruleus and ventral tegmental area

AU - González, J Antonio

AU - Jensen, Lise T

AU - Fugger, Lars

AU - Burdakov, Denis

N1 - Acknowledgements This work was funded by the European Research Council (FP7)

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N2 - 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.

AB - 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.

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KW - Locus Coeruleus

KW - Mice

KW - Mice, Transgenic

KW - Microscopy, Confocal

KW - Microspheres

KW - Neural Pathways

KW - Neurons

KW - Neuropeptides

KW - Orexins

KW - Rhodamines

KW - Ventral Tegmental Area

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

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