Does the Glutamate Amplifies Noradrenergic Effects (GANE) model help explain why we fail to remember our dreams? Acetylcholine and norepinephrine balance in wakefulness and rapid-eye-movement (REM) sleep

The ascending fibers releasing norepinephrine (NE) and acetylcholine (ACh) are highly active during wakefulness. In contrast, during REM sleep, the neocortical tone is mainly sustained by ACh. By comparing the different physiological features of the NE and ACh systems in the light of the GANE model, we suggest how to interpret some functional differences between waking and REM sleep. Regulation of neocortical circuits by ascending regulatory systems involves all of the classic neurotransmitters. Most of the nuclei located in brainstem, hypothalamus and basal forebrain are not only reciprocally connected, but send direct projections to the neocortex (Steriade & McCarley 2005; Saper et al. 2010; Jones 2011). The same applies to the hypothalamic nuclei releasing neuropeptides such as orexin/hypocretin (in wakefulness) and melanin concentrating hormone, MCH (in REM sleep; Jones & Hassani 2008; Monti et al. 2013; Aracri et al. 2013, and references therein). As a first approximation, these bewildering intricacies can be simplified by focusing on the balance between the activity of noradrenergic and cholinergic nuclei, which are crucial regulators of arousal and cognition (e.g., Constantinople & Bruno 2011; Schmidt et al. 2013). Both project varicose fibers that widely innervate the neocortex, and their global effects are excitatory. During wakefulness, high levels of NE and ACh cooperate in regulating Commentary Article Click here to download Commentary Article 11-8-15_27-Mather.doc