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Nat Neurosci. 2010 Oct;13(10):1190-8. doi: 10.1038/nn.2623. Epub 2010 Sep 5.

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

Author information

1
Case Western Reserve University, School of Medicine, Department of Neurosciences, Cleveland, Ohio, USA.

Abstract

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.

PMID:
20818386
PMCID:
PMC2947586
DOI:
10.1038/nn.2623
[Indexed for MEDLINE]
Free PMC Article

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