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Nitric oxide modulates the discharge rate of basal forebrain neurons

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Abstract

Rationale

During prolonged wakefulness, the concentrations of nitric oxide (NO) and adenosine (AD) increase in the basal forebrain (BF). AD inhibits neuronal activity via adenosine (A1) receptors, thus providing a potential mechanism for sleep facilitation. Although NO in the BF increases adenosine and promotes sleep, it is not clear whether the sleep promotion by NO is mediated through adenosine increase, or NO independently of adenosine could modulate sleep.

Objective

The objective of the study was to clarify whether NO modulates the discharge rate of BF neurons and whether this effect is mediated via AD.

Materials and methods

We measured the discharge rates of BF neurons in anesthetized rats during microdialysis infusion of NO donor alone or in combination with A1 receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine.

Results

NO dose dependently modulated the discharge rate of BF neurons. NO donor (0.5 mM) increased the discharge rates in 48% of neurons and decreased it in 22%. A 1-mM dose decreased it in 55% and increased in 18%. Tactile stimulus affected the discharge rates of most neurons: 60% increased (stimulus-on) it and 14% decreased it (stimulus-off). A 1-mM NO donor predominantly inhibited neurons of both stimulus related types. A small proportion of stimulus-on (23%) neurons but none of the stimulus-off neurons were activated by NO donor. The blockade of A1 receptors partly prevented the inhibitory effect of NO on most of the neurons. This response was more prominent in stimulus-on than in stimulus-off neurons.

Conclusion

NO modulates the BF neuronal discharge rates in a dose-dependent manner. The inhibitory effect is partly mediated via adenosine A1 receptors.

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Abbreviations

AD:

adenosine

BF:

basal forebrain

BL:

base line

CPT:

8-Cyclopentyl-1,3-dimethylxanthine

CSF:

artificial cerebrospinal fluid

EEG:

electroencephalogram

fEPSP:

focal excitatory post-synaptic potential

GABA:

gamma-aminobutyric acid

GMP:

guanidine mono-phosphate

HDB:

horizontal diagonal band of Broca

HPLC:

high-performance liquid chromatography

MCPO:

magnocellular preoptic nucleus

NO:

nitric oxide

NOC-18:

(DETA/NO); 2,2’-(hydroxynitrosohydrazino)bis-ethanamine

eNOS, nNOS, and iNOS:

endothelial, neuronal, and inducible nitric oxide synthetase, respectively

REM:

rapid eye movement

SD:

standard deviation

SI:

substantia innominata

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Acknowledgements

This study was funded by the European Union grants MCRTN-CT-2004-512362 and LSHM-CT-2005-518189 and the Academy of Finland

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Authors and Affiliations

  1. Institute of Biomedicine, University of Helsinki, P.O. Box 63, 00014, Helsinki, Finland

    Andrey Kostin, Dag Stenberg, Anna V. Kalinchuk & Tarja Porkka-Heiskanen

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  1. Andrey Kostin
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  2. Dag Stenberg
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  3. Anna V. Kalinchuk
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  4. Tarja Porkka-Heiskanen
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Corresponding author

Correspondence to Tarja Porkka-Heiskanen.

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Table 1

Time-dependent decrease in the BF adenosine concentration after probe insertion (n = 4); mean ± SD (DOC 14.6 KB)

Fig. 4g

The discharge rate (spikes/10 s) of single neurons, which were phasically increased during early period of NO-donor infusion but later decreased to the level lower then during the BL. The last two diagrams are exceptions, where discharge rate was, respectively, not different or higher as compared to BL level (GIF 8.67 MB).

High resolution image file (TIFF 4.61 MB).

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Kostin, A., Stenberg, D., Kalinchuk, A.V. et al. Nitric oxide modulates the discharge rate of basal forebrain neurons. Psychopharmacology 201, 147–160 (2008). https://doi.org/10.1007/s00213-008-1257-x

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