Pal Dinesh, Mallick Birendra Nath
School of Life Sciences, Jawaharlal Nehru University, New Delhi 110 067, India.
Neuropharmacology. 2006 Jul;51(1):1-11. doi: 10.1016/j.neuropharm.2006.02.006. Epub 2006 Apr 17.
Rapid eye movement (REM) sleep disturbance is associated with several psycho-behavioral disorders, hence, it is important to understand its neural mechanism of regulation. Although it was known that the noradrenergic (NA-ergic) neurons from locus coeruleus (LC) project to the pedunculopontine tegmentum (PPT), the role of noradrenaline (NA) alone and in association with GABA, an inhibitory neurotransmitter, in PPT for REM sleep regulation was not known and was investigated in this study in freely moving normally behaving rats. Rats were surgically prepared for electrophysiological sleep-wake recording and simultaneous bilateral microinjections into PPT. 200nl of prazosin (alpha1-antagonist) or clonidine (alpha2-agonist) or propranolol (beta-antagonist) or combination of picrotoxin (GABA-A antagonist) and clonidine or vehicle (control) was microinjected bilaterally into PPT using a remote-controlled pump and the effects on REM sleep compared. Prazosin, clonidine and propranolol increased the total time spent in REM sleep whereas co-injection of picrotoxin and clonidine did not affect REM sleep. The results suggest that NA in PPT tonically inhibits REM sleep, possibly by acting on the cholinergic REM-ON neurons, while GABA inhibits the release of NA for REM sleep regulation. A model of neural connections explaining such regulation has been presented.
快速眼动（REM）睡眠障碍与多种心理行为障碍有关，因此，了解其神经调节机制很重要。虽然已知来自蓝斑（LC）的去甲肾上腺素能（NA能）神经元投射到脚桥被盖核（PPT），但单独的去甲肾上腺素（NA）以及与抑制性神经递质GABA联合在PPT中对REM睡眠调节的作用尚不清楚，本研究在自由活动的正常行为大鼠中对此进行了研究。对大鼠进行手术准备以进行电生理睡眠-觉醒记录，并同时向PPT进行双侧微量注射。使用遥控泵将200nl的哌唑嗪（α1拮抗剂）或可乐定（α2激动剂）或普萘洛尔（β拮抗剂）或印防己毒素（GABA-A拮抗剂）与可乐定的组合或溶剂（对照）双侧微量注射到PPT中，并比较对REM睡眠的影响。哌唑嗪、可乐定和普萘洛尔增加了REM睡眠的总时长，而印防己毒素与可乐定共同注射则不影响REM睡眠。结果表明，PPT中的NA可能通过作用于胆碱能REM-ON神经元来持续抑制REM睡眠，而GABA则抑制NA的释放以调节REM睡眠。本文提出了一个解释这种调节的神经连接模型。
