GABAB receptor-mediated tonic inhibition regulates the spontaneous firing of locus coeruleus neurons in developing rats and in citalopram-treated rats

Han Ying Wang, Zhao Chen Kuo, Yu Show Fu, Ruei Feng Chen, Ming Yuan Min, Hsiu Wen Yang*

*此作品的通信作者

研究成果: Article同行評審

17 引文 斯高帕斯(Scopus)

摘要

Noradrenaline (NA)-releasing neurons in the locus coeruleus (LC) provide NA to the forebrain. Their activity is believed to be a key factor regulating the wakefulness/arousal level of the brain. In this study, we found that the activity of NA-releasing neurons in the LC (LC neurons) was subject to γ-aminobutyric acid (GABA) tonic inhibition through GABAB receptors (GABABRs), but not GABAA receptors. The intensity of GABABR tonic inhibition was found to depend on ambient GABA levels, as it was dramatically increased by blockade of GABA reuptake. It also varied with the function of GABABRs. The GABABR activity on LC neurons was found to increase with postnatal age up to postnatal days 8-10, resulting in increased tonic inhibition. Interestingly, there was no significant difference in the spontaneous activity of LC neurons at different postnatal ages unless GABABR tonic inhibition was blocked. These results show that, during postnatal development, there is a continuous increase in GABABR tonic inhibition that maintains the activity of LC neurons at a proper level. In male, but not female, rats, chronic perinatal treatment with citalopram, a selective serotonin reuptake inhibitor, reduced GABABR activity and tonic inhibition, which might result in the significantly higher spontaneous activity of LC neurons seen in these animals. In conclusion, our results show that GABABR-mediated tonic inhibition has a direct impact on the spontaneous activity of LC neurons and that the extent of the effect varies with ambient GABA levels and functionality of GABABR signalling.

原文English
頁(從 - 到)161-180
頁數20
期刊Journal of Physiology
593
發行號1
DOIs
出版狀態Published - 1 1月 2015

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