Neurotrophin Receptor Ntrk2b Function In The Maintenance Of Dopamine And Serotonin Neurons In Zebrafish

Brain-derived neurotrophic factor (BDNF), together with its cognate receptor tyrosine kinase B (TrkB), plays an essential role in the development and plasticity of the brain and is widely implicated in psychiatric diseases (Autry and Monteggia, 2012). Due to the highly conserved evolutionary lineage of neurotrophins and their receptors in vertebrates, the zebrafish is a well-suited model for this study. The TrkB receptor, also known as NTRK2, has two forms in zebrafish, Ntrk2a and Ntrk2b. The spatio-temporal expression pattern of bdnf and ntrk2b in zebrafish was studied using in situ hybridization. The complementary expression pattern of ntrk2b to bdnf suggests that ntrk2b is the key receptor, unlike its duplicate isoform ntrk2a. Two reverse genetics strategies, morpholino oligonucleotides (MO) and the TILLING mutant, were applied in this study. The loss or complete deletion of ntrk2b had no major effect on the viability, gross phenotype, or swimming behavior of zebrafish. A specific subset of the dopaminergic and serotonergic neuronal population was affected in the morphants and mutants. Downstream signaling transcripts such as bdnf, serta, th2, and tph2 were downregulated and could be rescued by overexpression of the full-length ntrk2b mRNA in the morphants. Pharmacological intervention with a tyrosine kinase inhibitor, K252a, resulted in similar phenotypes. Overall, our results reveal a specific effect of ntrk2b on the two crucial aminergic systems involved in psychiatric disorders and provide an essential tool to study neurotrophin function in modulating neuronal plasticity in the central nervous system.