ArticleNeuron2015
A genome-wide screen identifies PAPP-AA-mediated IGFR signaling as a novel regulator of habituation learning.
Article in Neuron, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 61 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
61 citing papers in PubMed, 102 citations in OpenAlex.
- zAcademy: an open-source programmable conditioning arena reveals sex- and genotype-dependent avoidance learning in adult zebrafish.bioRxiv : the preprint server for biology · 2026Article
- StrIPETrack: a real-time, ROI-flexible tracking platform for high-throughput zebrafish behavior.Biology open · 2026Article
- Inhibition of Cxcr4 chemokine receptor signaling improves habituation learning in a zebrafish model of neurofibromatosis.Disease models & mechanisms · 2026Article
- Article
- CaMPARI2 enables stimulus-locked whole-brain activity mapping at cellular resolution in unrestrained larval zebrafish.Frontiers in molecular neuroscience · 2026Article
- Induced epileptic seizures in larval zebrafish reveal a synaptic modulation associated with the post-ictal state.Brain communications · 2026Article
- CaMPARI2 Enables Stimulus-Locked Whole-Brain Activity Mapping at Cellular Resolution in Unrestrained Larval Zebrafish.bioRxiv : the preprint server for biology · 2025Article
- Phenotype to genotype: A new and rapid approach using whole-genome sequencing.PLoS genetics · 2025Article
- Cadherin-16 regulates acoustic sensory gating in zebrafish through endocrine signaling.PLoS biology · 2025Article
- Habituation learning: insights from zebrafish larvae.Frontiers in molecular neuroscience · 2025Review
- Cadherin 16 promotes sensory gating via the endocrine corpuscles of Stannius.bioRxiv : the preprint server for biology · 2024Article
- The adaptor protein 2 (AP2) complex modulates habituation and behavioral selection across multiple pathways and time windows.iScience · 2024Article
- Context-dependent hyperactivity inFrontiers in molecular neuroscience · 2024Article
- A single base pair substitution in zebrafish distinguishes between innate and acute startle behavior regulation.PloS one · 2024Article
- Loss-of-function variants in MYCBP2 cause neurobehavioural phenotypes and corpus callosum defects.Brain : a journal of neurology · 2023Article
- Integration of cooperative and opposing molecular programs drives learning-associated behavioral plasticity.PLoS genetics · 2023Article
- The calcium-sensing receptor (CaSR) regulates zebrafish sensorimotor decision making via a genetically defined cluster of hindbrain neurons.Cell reports · 2022Article
- Chemokine signaling synchronizes angioblast proliferation and differentiation during pharyngeal arch artery vasculogenesis.Development (Cambridge, England) · 2022Article
- Zebrafish models of alx-linked frontonasal dysplasia reveal a role for Alx1 and Alx3 in the anterior segment and vasculature of the developing eye.Biology open · 2022Article
- Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Habituation represents a fundamental form of learning, yet the underlying molecular genetic mechanisms are not well defined. Here we report on a genome-wide genetic screen, coupled with whole-genome sequencing, that identified 14 zebrafish startle habituation mutants including mutants of the vertebrate-specific gene pregnancy-associated plasma protein-aa (pappaa). PAPP-AA encodes an extracellular metalloprotease known to increase IGF bioavailability, thereby enhancing IGF receptor signaling. We find that pappaa is expressed by startle circuit neurons, and expression of wild-type but not a metalloprotease-inactive version of pappaa restores habituation in pappaa mutants. Furthermore, acutely inhibiting IGF1R function in wild-type reduces habituation, while activation of IGF1R downstream effectors in pappaa mutants restores habituation, demonstrating that pappaa promotes learning by acutely and locally increasing IGF bioavailability. In sum, our results define the first functional gene set for habituation learning in a vertebrate and identify PAPPAA-regulated IGF signaling as a novel mechanism regulating habituation learning.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.