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 language | English |
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Pages (from-to) | 1426-1432 |
Number of pages | 7 |
Journal | European Journal of Neuroscience |
Volume | 35 |
Issue number | 9 |
Early online date | 16 Apr 2012 |
DOIs | |
Publication status | Published - May 2012 |
Bibliographical note
AcknowledgementsThis work was funded by the European Research Council (FP7)
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