Inactivation of median preoptic nucleus causes c-Fos expression in hypocretin- and serotonin-containing neurons in anesthetized rat.
The median preoptic nucleus (MnPN) of the hypothalamus contains sleep-active neurons including sleep-active GABAergic neurons and is involved in the regulation of nonREM/REM sleep. The hypocretinergic (HCRT) neurons of the perifornical-lateral hypothalamic area (PF-LHA) and serotonergic (5-HT) neurons of the dorsal raphe nucleus (DRN) are mostly active during waking and have been implicated in the regulation of arousal. MnPN GABAergic neurons project to the PF-LHA and DRN. It is hypothesized that MnPN promotes sleep by inhibiting multiple arousal systems including HCRT and other wake-active neurons within the PF-LHA and 5-HT neurons in the DRN. We examined the effects of inactivation of MnPN neurons by locally microinjecting 0.2 microl of 1 mM or 10 mM solutions of a GABA(A) receptor agonist, muscimol, into the MnPN on Fos expression (Fos-IR) in the PF-LHA neurons including HCRT neurons and 5-HT neurons in the DRN in anesthetized rats. Compared to artificial cerebrospinal fluid control, microinjection of muscimol into the MnPN resulted in significantly higher percentages of HCRT and non-HCRT neurons in the PF-LHA and 5-HT neurons in the DRN that exhibited Fos-IR. The percentage of melanin-concentrating hormone (MCH)+/Fos+ neurons in the PF-LHA did not change after muscimol treatments. These results support a hypothesis that the activation of MnPN neurons contributes to the suppression of wake-promoting systems including HCRT and other unidentified neurons in the PF-LHA and 5-HT neurons in the DRN. These results also suggest that MCH neurons may not be under MnPN inhibitory control. These findings are consistent with a hypothesized role of MnPN in sleep regulation.
Kumar
Sunil
S
Research Service, Veteran Affairs Greater Los Angeles Healthcare System, 16111 Plummer Street, Sepulveda, California 91343, USA.
Szymusiak
Ronald
R
Bashir
Tariq
T
Suntsova
Natalia
N
Rai
Seema
S
McGinty
Dennis
D
Alam
Md Noor
MN
D000758:Anesthesia; D000818:Animals; D001143:Arousal / Q000502:physiology; D002452:Cell Count; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D005786:Gene Expression Regulation / Q000502:physiology*; D016762:Genes, fos / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007026:Hypothalamic Area, Lateral / Q000502:physiology; D007028:Hypothalamic Hormones / Q000378:metabolism; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008543:Melanins / Q000378:metabolism; D008845:Microinjections; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism / Q000502:physiology*; D064446:Orexin Receptors; D000068797:Orexins; D010907:Pituitary Hormones / Q000378:metabolism; D011301:Preoptic Area / Q000502:physiology*; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*
D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D007028:Hypothalamic Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D010907:Pituitary Hormones; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D009118:Muscimol; D012701:Serotonin; C019463:melanin-concentrating hormone; D005968:Glutamate Decarboxylase