Pet-1 is required across different stages of life to regulate serotonergic function

Transcriptional cascades are required for specification of 5-HT neurons and 5-HT modulated behaviors. Expression of several cascade factors extends across lifespan suggesting their control of behavior may not be temporally restricted to programming normal numbers of 5-HT neurons. We applied new mouse conditional targeting approaches to investigate ongoing requirements for Pet-1, a cascade factor required for the initiation of 5-HT synthesis but whose expression persists into adulthood. We found that Pet-1 was required after 5-HT neuron generation, for multiple steps in 5-HT neuron maturation including axonal innervation to the somatosensory cortex, firing properties, and 5-HT(1A) and 5-HT(1B) autoreceptor expression. Targeting Pet-1 in adult 5-HT neurons showed that it was still needed to preserve normal anxiety-related behaviors through direct autoregulated control of serotonergic gene expression. These findings show that Pet-1 is required across lifespan and therefore behavioral pathogenesis can result from both developmental and adult-onset alterations in serotonergic transcription.