SLEEP 2011 Abstract Supplement

A. Basic Science IV. Neurobiology
of inspiratory modulation of lingual EMG tended to be proportional to
the amplitude of diaphragmatic activity and inversely proportional to the
respiratory rate.
Conclusion: In rats, inspiratory modulation of lingual EMG is rare, of
low amplitude, and preferentially occurs during SWS. This suggests that
removal of wake- and REM sleep-related inputs to lingual motor output
facilitates transmission of inspiratory drive to hypoglossal motoneurons.
Support (If Any): HL-092962; DFG-Ste1899/1-1
0083
RATS SUBJECTED TO CHRONIC-INTERMITTENT
HYPOXIA (CIH) HAVE INCREASED DENSITY OF
NORADRENERGIC TERMINALS IN THE TRIGEMINAL
SENSORY (SP5) AND MOTOR (MO5) NUCLEI
Mody P, Rukhadze I, Kubin L
Department of Animal Biology, University of Pennsylvania,
Philadelphia, PA, USA
Introduction: Rodents subjected to CIH are used to investigate cardiorespiratory
and other consequences of obstructive sleep apnea (OSA).
We recently determined that rats subjected to CIH have increased density
of noradrenergic terminals in the hypoglossal nucleus (Mo12) which
innervates the muscles of the tongue that, in OSA patients, are hyperactive
and help maintain airway patency. Noradrenergic terminals in
the ventromedial Mo12 were nearly 40% more numerous in CIH than
sham-treated rats. We now investigated whether increased noradrenergic
innervation following CIH also occurs in other motor and sensory nuclei
of the brainstem.
Methods: CIH was administered for 10 h/day for 35 days, with oxygen
levels oscillating between 24% and 7% every 180 s. Six pairs of male
Sprague-Dawley rats were exposed to CIH or identically timed air exchanges.
Brainstems were cut into 35 μm transverse sections and immunohistochemically
processed for dopamine-β-hydroxylase. For each rat
in each pair, noradrenergic varicosities were counted in three sections in
100x100 μm counting boxes positioned at matching anteroposterior levels
in the center of Mo5 and three counting boxes placed at the nucleus
ambiguus level dorsoventrally and 100 μm medial to the lateral margin
of the interpolar part of Sp5.
Results: The average numbers of noradrenergic varicosities were much
higher in Mo5 than Sp5. In both locations, they were higher in CIH
than sham-treated rats (Mo5: 258±11(SE) in CIH and 236±10 in shamtreated
rats; n=18 section pairs, p=0.067, paired t-test; Sp5: 184±9 in
CIH and 156±8 in sham-treated rats; n=18, p=0.029).
Conclusion: Exposure to CIH results in 9-18% increased density of
noradrenergic terminals in the Mo5 and Sp5, suggesting that the effect
occurs in multiple functionally distinct nuclei. The increases in Mo5
were less prominent than those in Mo12, a difference possibly related to
stronger hypoxic stimulation of Mo12 than Mo5.
Support (If Any): HL-047600
0084
ROLE OF HYPOTHALAMIC GLUTAMATE AND GABA
RELEASE IN THE EFFECTS OF CAFFEINE ON HISTAMINE
NEURONS
John J 1,2 , Kodama T 3 , Siegel J 1,2
1
Neurobiology Res. 151 A3, VA Medical Center/Sepulveda Research
Corporation, North Hills, CA, USA, 2 Psychiatry, UCLA School of
Medicine, Los Angeles, CA, USA, 3 Psychology, Tokyo Metropolitan
Institute for Medical Research, Tokyo, Japan
Introduction: We hypothesized that the adenosine receptor antagonist
caffeine, the most widely used stimulant, increases glutamate release
and reduces GABA level in the tuberomammillary region and that this
underlies an activation of histamine (HA) neurons, thereby suppressing
sleep and promoting waking.
Methods: Male Sprague-Dawley rats were chronically implanted with
sleep-wake recording electrodes and cannulae for microdialysis probes.
After a one-week recovery period, microdialysis probes were inserted
through the guide cannulae to the PH-TMN. Microdialysis experiments
were performed between 10:00AM to 6.00PM (09:00AM lights-on:
09.00PM light-off) and were continuously perfused with aCSF at a flow
rate of 2µl/ min. We collected 10-minute samples starting two hours after
the beginning of the aCSF perfusion. Rats were given caffeine intraperitoneally
(25 mg/kg) and samples were collected from the PH-TMN
for 120 minutes after caffeine administration.
Results: HPLC analysis of the samples showed a significant increase
in glutamate levels after the caffeine treatment. Glutamate levels were
significantly elevated 30 min after caffeine administration and remained
high for an additional 90 minute period compared to pre-injection (F4,25
=10.9, P