Activity-dependent expression of Lmx1b regulates specification of serotonergic neurons modulating swimming behavior.

TitleActivity-dependent expression of Lmx1b regulates specification of serotonergic neurons modulating swimming behavior.
Publication TypeJournal Article
Year of Publication2010
AuthorsDemarque M, Spitzer NC
JournalNeuron
Volume67
Issue2
Pagination321-34
Date Published2010 Jul 29
ISSN1097-4199
KeywordsAction Potentials, Animals, Behavior, Animal, Bromodeoxyuridine, Calcium, Electroporation, Embryo, Nonmammalian, gamma-Aminobutyric Acid, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Homeodomain Proteins, Membrane Potentials, Neurons, Otx Transcription Factors, Potassium Channels, Inwardly Rectifying, Raphe Nuclei, RNA, Messenger, Serotonin, Sodium Channels, Statistics, Nonparametric, Swimming, Transcription Factors, Tryptophan Hydroxylase, Xenopus laevis, Xenopus Proteins
Abstract

Genetic programs, environmental factors, and electrical activity interact to drive the maturation of the brain. Although the cascade of transcription factors that leads to specification of the serotonergic phenotype has been well characterized, its interactions with electrical activity are not known. Here we show that spontaneous calcium spike activity in the hindbrain of developing Xenopus laevis larvae modulates the specification of serotonergic neurons via regulation of expression of the Lmx1b transcription factor. Activity acts downstream of Nkx2.2 but upstream of Lmx1b, leading to regulation of the serotonergic phenotype. Using global manipulation of activity and targeted alteration of Lmx1b expression, we also demonstrate that changes in the number of serotonergic neurons change larval swimming behavior. The results link activity-dependent regulation of a transcription factor to transmitter specification and altered behavior.

DOI10.1016/j.neuron.2010.06.006
Alternate JournalNeuron
PubMed ID20670838
PubMed Central IDPMC2913149
Grant ListNS15918 / NS / NINDS NIH HHS / United States
R01 NS015918 / NS / NINDS NIH HHS / United States
R01 NS015918-29 / NS / NINDS NIH HHS / United States
R01 NS015918-30 / NS / NINDS NIH HHS / United States
R01 NS015918-31 / NS / NINDS NIH HHS / United States
R01 NS015918-32 / NS / NINDS NIH HHS / United States
Category: 
Spitzer Laboratory