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ZFIN ID: ZDB-PUB-180419-7
A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold
Marsden, K.C., Jain, R.A., Wolman, M.A., Echeverry, F.A., Nelson, J.C., Hayer, K.E., Miltenberg, B., Pereda, A.E., Granato, M.
Date: 2018
Source: Cell Reports   23: 878-887 (Journal)
Registered Authors: Granato, Michael, Jain, Roshan, Marsden, Kurt, Wolman, Marc
Keywords: Cyfip2, GCaMP, Mauthner cell, acoustic startle response, behavior threshold, spiral fiber neurons, zebrafish
MeSH Terms:
  • 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*
PubMed: 29669291 Full text @ Cell Rep.
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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.
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