RRC ID 55008
Author Marsden KC, Jain RA, Wolman MA, Echeverry FA, Nelson JC, Hayer KE, Miltenberg B, Pereda AE, Granato M.
Title A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold.
Journal Cell Rep
Abstract Sensory experiences dynamically modify whether animals respond to a given stimulus, but it is unclear how innate behavioral thresholds are established. Here, we identify molecular and circuit-level mechanisms underlying the innate threshold of the zebrafish startle response. From a forward genetic screen, we isolated five mutant lines with reduced innate startle thresholds. Using whole-genome sequencing, we identify the causative mutation for one line to be in the fragile X mental retardation protein (FMRP)-interacting protein cyfip2. We show that cyfip2 acts independently of FMRP and that reactivation of cyfip2 restores the baseline threshold after phenotype onset. Finally, we show that cyfip2 regulates the innate startle threshold by reducing neural activity in a small group of excitatory hindbrain interneurons. Thus, we identify a selective set of genes critical to establishing an innate behavioral threshold and uncover a circuit-level role for cyfip2 in this process.
Volume 23(3)
Pages 878-887
Published 2018-4-17
DOI 10.1016/j.celrep.2018.03.095
PII S2211-1247(18)30471-6
PMID 29669291
PMC PMC6642828
MeSH Acoustic Stimulation Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism* Animals Axons / metabolism Behavior, Animal Calcium / metabolism Cytoskeleton / metabolism Excitatory Postsynaptic Potentials Fragile X Mental Retardation Protein / metabolism Hypersensitivity / metabolism Hypersensitivity / pathology Interneurons / metabolism* Larva / metabolism Mutagenesis Reflex, Startle / physiology Zebrafish / growth & development Zebrafish / metabolism Zebrafish Proteins / genetics Zebrafish Proteins / metabolism*
IF 7.815
Times Cited 6
Zebrafish Tol-056