Sleeping with the clock: pacemaker neurons enter the scene

Abstract

Theoretical contributions provided by Giuseppe Moruzzi in 1972 and Giovanni Berlucchi in 1970 are here revisited, highlighting an itinerary of knowledge on the relationships between sleep-wake alternation and biological clocks, and on the role of pacemaker neurons. With a modern insight, Moruzzi dealt with the role of homeostatic mechanisms and of “timing devices” in sleep and wake, and he referred to a theory formulated by Berlucchi. This theory, which has remained hidden in a book chapter, stemmed from a careful critical evaluation of previous experimental approaches and theories. With a remarkable intuition, Berlucchi proposed that the sleep-wake cycle is an endogenous biological rhythm, as other body rhythmic functions with which it interacts, and that this cycle is generated, as other rhythms, by a functional group of pacemaker neurons, endowed with endogenous rhythmic properties. Berlucchi viewed pacemaker neurons as hierarchically organized cells, entrained by the environment, controlled by intercellular, synaptic and nonsynaptic communication. All these hypotheses have been subsequently confirmed by discoveries that are here summarized. These issues are still at the forefront of research; many questions, however, are still open.