Highly specific role of hypocretin (orexin) neurons: differential activation as a function of diurnal phase, operant reinforcement versus operant avoidance and light level.
Hypocretin (Hcrt) cell loss is responsible for narcolepsy, but Hcrt's role in normal behavior is unclear. We found that Hcrt knock-out mice were unable to work for food or water reward during the light phase. However, they were unimpaired relative to wild-type (WT) mice when working for reward during the dark phase or when working to avoid shock in the light or dark phase. In WT mice, expression of Fos in Hcrt neurons occurs only in the light phase when working for positive reinforcement. Expression was seen throughout the mediolateral extent of the Hcrt field. Fos was not expressed when expected or unexpected unearned rewards were presented, when working to avoid negative reinforcement, or when given or expecting shock, even though these conditions elicit maximal electroencephalogram (EEG) arousal. Fos was not expressed in the light phase when light was removed. This may explain the lack of light-induced arousal in narcoleptics and its presence in normal individuals. This is the first demonstration of such specificity of arousal system function and has implications for understanding the motivational and circadian consequences of arousal system dysfunction. The current results also indicate that comparable and complementary specificities must exist in other arousal systems.
Veterans Administration Greater Los Angeles Healthcare System, Neurobiology Research (151A3), North Hills, California 91343, USA.
Ronald
R
McGregor
Ming-Fung
MF
Wu
Grace
G
Barber
Lalini
L
Ramanathan
Jerome M
JM
Siegel
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001921:Brain / Q000166:cytology; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D003216:Conditioning, Operant / Q000502:physiology*; D004326:Drinking / Q000235:genetics; D004435:Eating / Q000235:genetics; D004569:Electroencephalography; D004576:Electromyography; D004597:Electroshock / Q000009:adverse effects; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000378:metabolism*; D008027:Light / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000172:deficiency / Q000378:metabolism*; D000068797:Orexins; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D013057:Spectrum Analysis
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins