| RRC ID |
55008
|
| 著者 |
Marsden KC, Jain RA, Wolman MA, Echeverry FA, Nelson JC, Hayer KE, Miltenberg B, Pereda AE, Granato M.
|
| タイトル |
A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold.
|
| ジャーナル |
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.
|
| 巻・号 |
23(3)
|
| ページ |
878-887
|
| 公開日 |
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
|
| 引用数 |
6
|
| リソース情報 |
| ゼブラフィッシュ |
Tol-056
hspGFFDMC130A |
