Locus Coeruleus Acid-Sensing Ion Channels Modulate Sleep–Wakefulness and State Transition from NREM to REM Sleep in the Rat  

作　　者：Fayaz A.Mir Sushil K.Jha 

机构地区：[1]School of Life Sciences,Jawaharlal Nehru University,New Delhi 110067,India

出　　处：《Neuroscience Bulletin》2021年第5期684-700,共17页神经科学通报（英文版）

基　　金：supported by the Department of Science and Technology-Cognitive Science Initiative project funded to Sushil K Jha;support from Department of Biotechnology (DBT), Department of Science and Technology(PURSE), Universities for Potential of Excellence (UPOE Ⅱ) and University Grants Commission-Special Assistance Programme);JNU funds to Sushil K Jha。

摘　　要：The locus coeruleus(LC) is one of the essential chemoregulatory and sleep–wake(S–W) modulating centers in the brain. LC neurons remain highly active during wakefulness, and some implicitly become silent during rapid eye movement(REM) sleep. LC neurons are also involved in CO_2-dependent modulation of the respiratory drive. Acid-sensing ion channels(ASICs) are highly expressed in some brainstem chemosensory breathing regulatory areas, but their localization and functions in the LC remain unknown. Mild hypercapnia increases the amount of non-REM(NREM) sleep and the number of REM sleep episodes, but whether ASICs in the LC modulate S–W is unclear. Here, we investigated the presence of ASICs in the LC and their role in S–W modulation and the state transition from NREM to REM sleep. Male Wistar rats were surgically prepared for chronic polysomnographic recordings and drug microinjections into the LC. The presence of ASIC-2 and ASIC-3 in the LC was immunohistochemically characterized.Microinjections of amiloride(an ASIC blocker) and APETx2(a blocker of ASIC-2 and-3) into the LC significantly decreased wakefulness and REM sleep, but significantly increased NREM sleep. Mild hypercapnia increased the amount of NREM and the number of REM episodes. However, APETx2 microinjection inhibited this increase in REM frequency. These results suggest that the ASICs of LC neurons modulate S–W, indicating that ASICs could play an important role in vigilance-state transition. A mild increase in CO_2 level during NREM sleep sensed by ASICs could be one of the determinants of state transition from NREM to REM sleep.

关 键 词：Acid-sensing ion channels Carbon dioxide HYPERCAPNIA NREM sleep REM sleep 

分 类 号：R338.63[医药卫生—人体生理学]