Background
Adenosine, an ATP degradation product, is a sleep pressure factor. The adenosine 1 receptor (A1R) reports sleep need. Histaminergic neurons (HN) of the tuberomamillary nucleus (TMN) fire exclusively during wakefulness and promote arousal. All of them express GABAA receptors and are inhibited by GABA. Does adenosine contribute to their silencing? Subjects and treatment: Responses to adenosine were studied in mouse brain slices and primary dissociated cultures. For HN identification single-cell (sc)RT-PCR, reporter protein and pharmacology were used. Hippocampal Dentate Gyrus granular layer cells (DGgc) were studied in parallel.
Conclusions
Most HN are not inhibited by adenosine.
Methods
Firing frequency was recorded in patch-clamp configuration or by microelectrode arrays. A1R-expression was studied by scRT-PCR and semiquantitative PCR.
Results
Most DGgc were inhibited through A1R, detected with scRT-PCR in 7 out of 10 PDZd2-positive DGgc; all HN were A1R negative. One HN out of 25 was inhibited by adenosine. The A1R mRNA level in the hippocampus was 6 times higher than in the caudal (posterior) hypothalamus. Response to adenosine was weaker in hypothalamic compared to hippocampal cultures. Conclusions: Most HN are not inhibited by adenosine.