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 journalArticle

  • 1 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.

LanguageEnglish (US)
Pages878-887
Number of pages10
JournalCell Reports
Volume23
Issue number3
DOIs
StatePublished - Apr 17 2018

Fingerprint

Fragile X Mental Retardation Protein
Interneurons
Zebrafish
Startle Reflex
Genes
Electrophysiology
Rhombencephalon
Networks (circuits)
Acoustics
Animals
Genome
Phenotype
Imaging techniques
Mutation
Fibers
Proteins

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Marsden, K. C., Jain, R. A., Wolman, M. A., Echeverry, F. A., Nelson, J. C., Hayer, K. E., ... Granato, M. (2018). A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold. Cell Reports, 23(3), 878-887. https://doi.org/10.1016/j.celrep.2018.03.095

A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold. / Marsden, Kurt C.; Jain, Roshan A.; Wolman, Marc A.; Echeverry, Fabio A.; Nelson, Jessica C.; Hayer, Katharina E.; Miltenberg, Ben; Pereda, Alberto E.; Granato, Michael.

In: Cell Reports, Vol. 23, No. 3, 17.04.2018, p. 878-887.

Research output: Contribution to journalArticle

Marsden, KC, Jain, RA, Wolman, MA, Echeverry, FA, Nelson, JC, Hayer, KE, Miltenberg, B, Pereda, AE & Granato, M 2018, 'A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold' Cell Reports, vol. 23, no. 3, pp. 878-887. https://doi.org/10.1016/j.celrep.2018.03.095
Marsden KC, Jain RA, Wolman MA, Echeverry FA, Nelson JC, Hayer KE et al. A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold. Cell Reports. 2018 Apr 17;23(3):878-887. https://doi.org/10.1016/j.celrep.2018.03.095
Marsden, Kurt C. ; Jain, Roshan A. ; Wolman, Marc A. ; Echeverry, Fabio A. ; Nelson, Jessica C. ; Hayer, Katharina E. ; Miltenberg, Ben ; Pereda, Alberto E. ; Granato, Michael. / A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold. In: Cell Reports. 2018 ; Vol. 23, No. 3. pp. 878-887.
@article{ec109a0b92ec4e149a2b65b428ab3553,
title = "A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold",
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.",
keywords = "acoustic startle response, behavior threshold, Cyfip2, GCaMP, Mauthner cell, spiral fiber neurons, zebrafish",
author = "Marsden, {Kurt C.} and Jain, {Roshan A.} and Wolman, {Marc A.} and Echeverry, {Fabio A.} and Nelson, {Jessica C.} and Hayer, {Katharina E.} and Ben Miltenberg and Pereda, {Alberto E.} and Michael Granato",
year = "2018",
month = "4",
day = "17",
doi = "10.1016/j.celrep.2018.03.095",
language = "English (US)",
volume = "23",
pages = "878--887",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold

AU - Marsden, Kurt C.

AU - Jain, Roshan A.

AU - Wolman, Marc A.

AU - Echeverry, Fabio A.

AU - Nelson, Jessica C.

AU - Hayer, Katharina E.

AU - Miltenberg, Ben

AU - Pereda, Alberto E.

AU - Granato, Michael

PY - 2018/4/17

Y1 - 2018/4/17

N2 - 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.

AB - 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.

KW - acoustic startle response

KW - behavior threshold

KW - Cyfip2

KW - GCaMP

KW - Mauthner cell

KW - spiral fiber neurons

KW - zebrafish

UR - http://www.scopus.com/inward/record.url?scp=85045244159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045244159&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2018.03.095

DO - 10.1016/j.celrep.2018.03.095

M3 - Article

VL - 23

SP - 878

EP - 887

JO - Cell Reports

T2 - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 3

ER -