Seventy years ago Otto Loewi and Henry Dale shared the 1936 Nobel Prize for the discovery that acetylcholine (ACh) is a neurotransmitter. Loewi's Nobel Lecture provided the following historical context for their discovery (Loewi, 1936): “Up until the year 1921 it was not known how the stimulation of a nerve influenced the effector organ's function, in other words, in what way the stimulation was transmitted to the effector organ from the nerve-ending.” The significance of Loewi's and Dale's discovery is emphasized by the profound relevance of ACh for sensorimotor, autonomic, and arousal state control. At all neuromuscular junctions ACh is the transmitter. For the autonomic nervous system, all preganglionic sympathetic and parasympathetic nerves use ACh, as do postganglionic fibers of the parasympathetic nervous system. In the context of the present volume, the effector organ of sleep is the brain. Therefore, this chapter focuses on the role of cholinergic “nerve endings” through which “the effector organ” generates states of sleep and wakefulness. This chapter uses Loewi's synaptic perspective to review data from many laboratories demonstrating that cholinergic synaptic mechanisms (Fig. 5.1) regulate levels of arousal.
Blocking degradation of ACh activates the EEG and enhances REM sleep
The discovery of rapid eye movement (REM) sleep (Aserinsky & Kleitman, 1953) as a state of enhanced electroencephalographic (EEG) activity implied the existence of endogenous neurochemical mechanisms underlying rhythmic oscillations in brain excitability.