Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/136416

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

Priyadarshini Sahu, M.·Pajanoja, C.·Rozov, S.·Panula, P.·Castren, E.
View original source ↗Export metadata ↓

Abstract

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.\n\nSignificance StatementBrain-derived neurotrophic factor (BDNF) and its high-affinity receptor, tyrosine kinase (TrkB/NTRK2), play a major role in regulating the development and plasticity of neural circuits. Additionally, BDNF/TrkB signaling is involved in psychiatric disorders and antidepressant responses. This study presents the complementary gene expression pattern of TrkB and BDNF in zebrafish during the early larval stage and in the adult brain. Our results consistently indicate that BDNF/TrkB signaling has a significant role in the development and maintenance of dopaminergic and serotonergic neuronal populations. Therefore, the ntrk2b-deficient zebrafish model is well suited to studying psychiatric disorders attributed to a dysfunctional monoaminergic system, and could potentially be a valuable model for small molecule drug screening.

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Priyadarshini Sahu, M., Pajanoja, C., Rozov, S., Panula, P., Castren, E.. 2017-05-10. Neurotrophin Receptor Ntrk2b Function In The Maintenance Of Dopamine And Serotonin Neurons In Zebrafish. https://doi.org/10.1101/136416

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Sex differences in fear extinction are conditional, not categorical

Threat memories are dynamic, and their behavioral expression can change with subsequent experience and the passage of time. Extinction training can reduce conditioned fear responses, yet these responses may re-emerge over time through spontaneous recovery. Although biological sex has been implicated as modulatory factor in fear and extinction memory processes, studies have reported inconsistent findings. Here, we investigated how differences in extinction training and the timing of memory assessment influence extinction memory in male and female mice. Using contextual fear conditioning, we assessed fear acquisition and threat retention, characterized within-session and across-session extinction during repeated training, and compared shorter (3-minute) and longer (6-minute) daily extinction sessions. We subsequently evaluated extinction memory retention and spontaneous recovery at a later time point. Estrous-cycle stage in females was monitored daily throughout the experimental protocol to examine its potential association with fear and extinction behavior. We found that males and females demonstrated comparable fear acquisition and threat memory, as well as similar extinction progression across days. During longer extinction sessions, but not shorter, males showed greater within-session reductions in freezing, whereas females exhibited modestly higher overall freezing. We found no significant sex difference in the magnitude of spontaneous recovery. There was no significant association between estrous-cycle stage and freezing behavior. Together, our findings suggest that sex-dependent differences in contextual fear extinction are not uniformly expressed, but rather depend on the experimental conditions under which extinction is assessed

neuroscience↗
bioRxiv2026

LAMA2-related muscular dystrophy alters Schwann cell calcium homeostasis and increases peripheral nerve inflammation

LAMA2-related muscular dystrophy (LAMA2-RD) affects skeletal muscle and peripheral nerves, yet the consequences of LAMA2 deficiency on peripheral nerve integrity beyond early postnatal development remain incompletely understood. We investigated sciatic nerve architecture and molecular alterations across postnatal life in hypomorphic Lama2dy2J/dy2J mice. LAMA2 localizes around the abaxonal surface of myelinating Schwann cells in control nerves. LAMA2-deficient nerves exhibited patchy regions lacking myelinated axons from early postnatal stages into adulthood, including expanded Remak bundles along with axons completely lacking normal Schwann cell ensheathment. In adult nerves, myelin infolding and reduced myelin circularity revealed abnormalities in the architecture of myelin that had formed. Bulk sciatic nerve RNA sequencing identified altered calcium-signaling and immune-related transcriptional signatures. Complementary Fura Red measurements in primary nerve-derived Schwann cell cultures demonstrated decreased intracellular calcium in LAMA2-deficient samples, while ATP-evoked responses were preserved. Older LAMA2-deficient nerves also exhibited increased CD45+CD11b+ myeloid-cell infiltration. Together, these observations extend the characterization of LAMA2-associated neuropathy into adulthood and identify calcium homeostasis and neuroimmune responses as candidate processes relevant to persistent peripheral nerve pathology.

neuroscience↗
bioRxiv2026

Endothelin-1 from Tongue Glands Gates 1 Sodium Taste and Intake

Sodium is an essential nutrient. To survive sodium deficiency, animals dramatically increase their appetite for salt. However, whether and how sodium depletion impacts the taste of salt to drive sodium intake is unknown. Here we show that tongue gland-derived endothelin-1 (EDN1) regulates the amiloride-sensitive, sodium-selective salt taste. Edn1 is specifically expressed in the glands embedded within the tongue. Under normal conditions, EDN1 suppresses salt taste by acting on its receptor EDNRB on the projections of salt-sensing taste neurons innervating taste buds. When internal sodium levels drop, EDN1 expression decreases, lifting this inhibition and enhancing responses to salt. Applying EDN1 directly to the tongue, using a nonionic eutectic-based organogel (Neogel) delivery technology that we establish here, dampens the activity of the salt-sensing taste neurons and reduces salt intake and preference. Conversely, genetic deletion of Ednrb in taste neurons mimics the effects of sodium deficiency, enhancing salt-sensing neuron activity and increasing salt consumption. These findings reveal a peripheral mechanism that regulates salt taste and intake in response to internal sodium levels, highlighting a direct role of the taste pathway in maintaining nutrient homeostasis.

neuroscience↗