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Our understanding of the molecular mechanisms underlying sleep homeostasis is limited. We have taken a systematic approach to study neural signaling by the transmitter 5-hydroxytryptamine (5-HT) in drosophila. We have generated knockout and knockin lines for  Trh , the 5-HT synthesizing enzyme and all five 5-HT receptors, making it possible for us to determine their expression patterns and to investigate their functional roles. Loss of the  Trh ,  5HT1a  or  5HT2b  gene decreased sleep time whereas loss of the  Trh  or  5HT2b  gene diminished sleep rebound after sleep deprivation.  5HT2b  expression in a small subset of, probably a single pair of, neurons in the dorsal fan-shaped body (dFB) is functionally essential: elimination of the  5HT2b  gene from these neurons led to loss of sleep homeostasis. Genetic ablation of 5HT2b neurons in the dFB decreased sleep and impaired sleep homeostasis. Our results have shown that serotonergic signaling in specific neurons is required for the regulation of sleep homeostasis.

Sleep homeostasis regulated by 5HT2b receptor in a small subset of neurons in the dorsal fan-shaped body of drosophila