Effects of adenosine on gabaergic synaptic inputs to identified ventrolateral preoptic neurons.
The ventrolateral preoptic nucleus (VLPO) is a key regulator of behavioral state that promotes sleep by directly inhibiting brain regions that maintain wakefulness. Subarachnoid administration of adenosine (AD) or AD agonists promotes sleep and induces expression of Fos protein in VLPO neurons. Therefore, activation of VLPO neurons may contribute to the somnogenic actions of AD. To define the mechanism through which AD activates VLPO neurons, we prepared hypothalamic slices from 9 to 12-day-old rat pups and recorded from 43 neurons in the galaninergic VLPO cluster; nine neurons contained galanin mRNA by post hoc in situ hybridization. Bath application of AD (20 microM) to seven of these neurons had no direct effect but caused a significant decrease in the frequency of spontaneous miniature inhibitory postsynaptic currents in the presence of tetrodotoxin, indicating a presynaptic site of action. We conclude that AD-mediated disinhibition increases the excitability of VLPO neurons thus contributing to the somnogenic properties of AD.
Chamberlin
N L
NL
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institute of Medicine, Room 820, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. nchamber@caregroup.harvard.edu
Arrigoni
E
E
Chou
T C
TC
Scammell
T E
TE
Greene
R W
RW
Saper
C B
CB
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000344:Afferent Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D019004:Galanin / Q000235:genetics; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D012333:RNA, Messenger; D005680:gamma-Aminobutyric Acid; D019004:Galanin; D000241:Adenosine