A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold

Kurt C. Marsden, Roshan A. Jain, Marc A. Wolman, Fabio A. Echeverry, Jessica C. Nelson, Katharina E. Hayer, Ben Miltenberg, Alberto E. Pereda, Michael Granato

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

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. Using forward genetics, electrophysiology, and combined behavior and Ca2+ imaging in zebrafish, Marsden et al. show that cyfip2 regulates the acoustic startle threshold by controlling the activity of excitatory spiral fiber interneurons.

Original languageEnglish (US)
Pages (from-to)878-887
Number of pages10
JournalCell Reports
Volume23
Issue number3
DOIs
StatePublished - Apr 17 2018

Keywords

  • Cyfip2
  • GCaMP
  • Mauthner cell
  • acoustic startle response
  • behavior threshold
  • spiral fiber neurons
  • zebrafish

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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