Inhibition of rostral basal forebrain neurons promotes wakefulness and induces FOS in orexin neurons.
The present study examined whether the activities of the rostral basal forebrain neurons alter the activities of the orexin (also known as hypocretin) neurons in the tuberal part of the hypothalamus in rats. We performed microdialysis perfusion of the ventromedial portion of the rostral basal forebrain with the GABAA receptor agonist muscimol to inhibit focally the neuronal activities in the rostral basal forebrain. Then, we monitored sleep/wake behaviour and investigated the pattern of activities of orexin neurons by examining the expression of FOS as an indicator of cellular activation. Bilateral perfusion with muscimol (5, 15, and 50 micro m) produced a dose-dependent decrease in the amount of sleep. This perfusion with muscimol at 50 micro m produced FOS-like immunoreactivity in 37% of the orexin neurons located in the tuberal part of the hypothalamus, whereas the FOS-like immunoreactivity was sparse in orexin neurons of the sleeping control rats (P = 0.001 by Mann-Whitney U-test). Unilateral perfusion with muscimol (50 micro m) also suppressed sleep. In this case, FOS-like immunoreactivity was seen in 40% of the orexin neurons on the side ipsilateral to the perfusion site but only in 10% of orexin neurons on the contralateral side (P = 0.018 by Wilcoxon signed rank test). These functional data suggested that a sleep-generating element in the ventromedial part of the rostral basal forebrain provides an inhibitory influence on the activities of the orexin neurons in the tuberal part of the hypothalamus.
Satoh
Shinsuke
S
Second Department of Anatomy and Neurobiology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan. satohs@med.kindai.ac.jp
Matsumura
Hitoshi
H
Nakajima
Tomoko
T
Nakahama
Ken-ichi
K
Kanbayashi
Tuyoshi
T
Nishino
Seiji
S
Yoneda
Hiroshi
H
Shigeyoshi
Yasufumi
Y
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002452:Cell Count; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D017551:Microdialysis; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D016761:Oncogene Proteins v-fos / Q000096:biosynthesis*; D000068797:Orexins; D017286:Polysomnography; D016548:Prosencephalon / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
D002352:Carrier Proteins; D018755:GABA Agonists; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D016761:Oncogene Proteins v-fos; D000068797:Orexins; D009118:Muscimol