AUTHOR=Iwasaki Kanako , Komiya Haruna , Kakizaki Miyo , Miyoshi Chika , Abe Manabu , Sakimura Kenji , Funato Hiromasa , Yanagisawa Masashi 

TITLE=Ablation of Central Serotonergic Neurons Decreased REM Sleep and Attenuated Arousal Response

JOURNAL=Frontiers in Neuroscience

VOLUME=12

YEAR=2018

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.00535

DOI=10.3389/fnins.2018.00535

ISSN=1662-453X

ABSTRACT=<p>Sleep/wake behavior is regulated by distinct groups of neurons, such as dopaminergic, noradrenergic, and orexinergic neurons. Although monoaminergic neurons are usually considered to be wake-promoting, the role of serotonergic neurons in sleep/wake behavior remains inconclusive because of the effect of serotonin (5-HT)-deficiency on brain development and the compensation for inborn 5-HT deficiency by other sleep/wake-regulating neurons. Here, we performed selective ablation of central 5-HT neurons in the newly developed <italic>Rosa-diphtheria toxin receptor (DTR)-tdTomato</italic> mouse line that was crossed with <italic>Pet1</italic><sup><italic>Cre</italic>/+</sup> mice to examine the role of 5-HT neurons in the sleep/wake behavior of adult mice. Intracerebroventricular administration of diphtheria toxin completely ablated tdTomato-positive cells in <italic>Pet1</italic><sup><italic>Cre</italic>/+</sup><italic>; Rosa-DTR-tdTomato</italic> mice. Electroencephalogram/electromyogram-based sleep/wake analysis demonstrated that central 5-HT neuron ablation in adult mice decreased the time spent in rapid eye movement (REM) sleep, which was associated with fewer transitions from non-REM (NREM) sleep to REM sleep than in control mice. Central 5-HT neuron-ablated mice showed attenuated wake response to a novel environment and increased theta power during wakefulness compared to control mice. The current findings indicated that adult 5-HT neurons work to support wakefulness and regulate REM sleep time through a biased transition from NREM sleep to REM sleep.</p>