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

• DOI: 10.1038/nn.2623
• Publication Date: 2010-09-05T19:03:18Z
• Authors: Chen Liu; Takashi Maejima; Steven C Wyler; Gemma Casadesus; Stefan Herlitze; Evan S Deneris
• Keywords: Male; Neurons; 8-Hydroxy-2-(di-n-propylamino)tetralin; Analysis of Variance; Chromatin Immunoprecipitation; Extracellular Matrix Proteins; 0303 health sciences; Age Factors; Estrogen Antagonists; Gene Expression Regulation, Developmental; Cell Differentiation; Mice, Transgenic; In Vitro Techniques; Motor Activity; Article; Mice, Inbred C57BL; Luminescent Proteins; Mice; 03 medical and health sciences; Animals, Newborn; Animals; Maze Learning; Excitatory Amino Acid Antagonists

Transcriptional cascades are required for the specification of serotonin (5-HT) neurons and behaviors modulated by 5-HT. Several cascade factors are expressed throughout the lifespan, which suggests that their control of behavior might not be temporally restricted to programming normal numbers of 5-HT neurons. We used new mouse conditional targeting approaches to investigate the ongoing requirements for Pet-1 (also called Fev), a cascade factor that is required for the initiation of 5-HT synthesis, but whose expression persists into adulthood. We found that Pet-1 was required after the generation of 5-HT neurons for multiple steps in 5-HT neuron maturation, including axonal innervation of the somatosensory cortex, expression of appropriate firing properties, and the expression of the Htr1a and Htr1b autoreceptors. Pet-1 was still required in adult 5-HT neurons to preserve normal anxiety-related behaviors through direct autoregulated control of serotonergic gene expression. These findings indicate that Pet-1 is required across the lifespan of the mouse and that behavioral pathogenesis can result from both developmental and adult-onset alterations in serotonergic transcription.