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Volume 17, Number 1,
Issue of January 1, 1997
pp. 420-427
Copyright ©1997 Society for Neuroscience
Nitric Oxide Production in Rat Thalamus Changes with Behavioral
State, Local Depolarization, and Brainstem Stimulation
Received July 24, 1996; revised Oct. 3, 1996; accepted Oct. 9, 1996.
Julie A. Williams,
Steven R. Vincent, and
Peter B. Reiner
Kinsmen Laboratory of Neurological Research, Department of
Psychiatry, Graduate Program in Neuroscience, University of British
Columbia, Vancouver, British Columbia, Canada V6T 1Z3
Since its discovery as a putative neurotransmitter in the CNS,
several functional roles have been suggested for nitric oxide (NO).
However, few studies have investigated the role of NO in natural
physiology. Because NO synthase (NOS) has been localized in regions
believed to be important for attention and arousal, we hypothesized
that NO production would be state-dependent. To test this hypothesis,
we used in vivo microdialysis, coupled with the
hemoglobin-trapping technique, to monitor extracellular NO concentrations in rat thalamus during wake, slow-wave sleep (SWS), and
rapid eye movement (REM) sleep. The thalamus is known to receive a
massive innervation from the NOS/cholinergic neurons in the mesopontine
brainstem, which have been suggested to play a key role in EEG
desynchronized states. To test whether thalamic NO output was sensitive
to neuronal-dependent changes in the mesopontine brainstem, we measured
thalamic NO concentration in response to electrical stimulation in the
laterodorsal tegmentum (LDT) of anesthetized rats. Finally, the calcium
dependence of NO release was tested by local depolarization with a high
potassium dialysate or by addition of a calcium chelator. The results
showed that (1) extracellular NO concentrations in the thalamus were
high during wake and REM sleep and significantly lower during SWS, (2)
thalamic NO release increased in response to LDT stimulation in both a
site-specific and tetrodotoxin (TTX)-dependent manner, and (3) NO
production was calcium-dependent. These data suggest that thalamic NO
production may play a role in arousal.
Key words:
nitric oxide;
sleep;
arousal;
microdialysis;
mesopontine
cholinergic neurons;
EEG
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