Regulation Of Sleep-Wake Behavior By Cholinergic Basal Forebrain Neurons

The basal forebrain (BF) plays an important and diverse roles in the modulation of cortical activity in association with different behavioral states. Previous studies reported that the BF plays a crucial role in increasing cortical activation during rapid eye movement (REM) sleep and wakefulness. However, the exact role of cholinergic BF (ch-BF) neurons in the sleep-wake cycle remains unclear. As the optogenetics is more and more widely used in neuroscience we can manipulate the ch-BF neurons with a high spatial and temporal resolution and specificity. The choline acetyltransferase (ChAT) is synthetase of acetyl choline and usually used as the marker of cholinergic neurons. In ChAT-ChR2-EYFP mice, the expression of exogenous gene ChR2-EYFP is controlled by ChAT promotor, so ChR2-EYFP could specifically expression in the cholinergic neurons. Here I used ChAT-ChR2-EYFP mice to study the role of ch-BF neurons in sleep-wake transitions which were activated by blue illumination.Firstly, I photostimulated the ch-BF neurons in ChAT-ChR2-EYFP mice duing active period and inactive period and found15s photostimulation could induce an immediate transition to waking or REM sleep from slow-wave sleep (SWS), but not most likely to induce behavioral arousal from REM sleep. Conversely, there was a significantly decreased probability of transition to wakefulness from REM sleep during photostimulation in the ChAT-ChR2-EYFP mice. Furthermore, photostimulation of ch-BF neurons during the waking and REM sleep prolonged their durations. Although activation of ch-BF neurons promoted SWS-to-waking and SWS-to-REM sleep transition, photostimulation may only facilitate the SWS transition to the next episode of wakefulness or REM sleep, but did not change the fate of the transition. Meanwhile the electroencephalographic (EEG) power was analyzed and I found that the total theta power (4-10Hz) of the light-induced waking or REM sleep was not significantly different from that of natural waking or REM sleep. However, when the theta component was divided into two bands, I found that the low theta power (4-7Hz) of the light-induced REM sleep was slightly increased, whereas the high theta power (7-10Hz) of the light-induced waking or REM sleep was significantly decreased as compared with natural wakefulness or REM sleep. I also found that1h long term photostimulation during the active period or inactive period in the ChAT-ChR2-EYFP mice could significantly increase the amount of wakefulness and decrease the amount of SWS in the following24h which mainly occurred in the subsequent inactive period.In conclusion, the ch-BF neurons have an important role in promoting wake and REM sleep. Photostimulation during SWS evoked transitions to wake or REM sleep and facilitated transitions from SWS, but did not change the fate of the transition. Photostimulation during REM sleep did not immediately induce transitions to wake and prolonged photostimulation induced a delayed insomnia-like behavior.