Dopamine neurons in the ventral tegmental area modulate rapid eye movement sleep

Abstract

The commentaries from Drs. Fraigne, Luppi, Mahoney, De Luca, Shiromani, and Weber highlight the strengths, limitations, and new insights that Hasegawa et al.'s findings provide in the field of sleep science, and our understanding of rapid eye movement (REM) sleep control. A common theme that emerged was that Hasegawa et al.'s study adds to the growing body of evidence that REM sleep is controlled by a distributed network of circuits located throughout the brain. Research over the last 20 years has identified neurons in the medulla, pons, hypothalamus, and midbrain in REM sleep control. Hasegawa et al.'s study, now indicate that dopamine neurons in the ventral tegmental area and dopamine receptor-expressing neurons in the basolateral amygdala also contribute to the modulation of REM sleep. Another common theme raised by commentators was-how do dopamine receptor-expressing neurons in the basolateral amygdala communicate with the pontine neurons that generate REM sleep? Although it has been more than 60 years since Jouvet's seminal work suggested that neural structures in the pons generate REM sleep, the principle pontine neurons responsible for generating REM sleep remain ambiguous. Although evidence indicates that neurons in the sublaterodorsal tegmental nucleus (a region that sits just beneath the locus coeruleus) are critical for REM sleep control, the transmitter phenotype(s) of these remains unclear. Evidence indicates that REM-generating neurons may be glutamatergic, GABAergic, or cholinergic in nature. Therefore, a central question in sleep biology is-which pontine neurons generate REM sleep? Answering this question will not only allow sleep scientists to understand how REM sleep is generated but it will also allow for a clearer determination of the functional hierarchy of the myriad of REM-modulating circuits that have been identified to date.