A Cyfip2-Dependent Excitatory Interneuron Pathway Establishes the Innate Startle Threshold
| Autor: | Roshan A. Jain, Fabio A. Echeverry, Ben Miltenberg, Alberto E. Pereda, Michael Granato, Kurt C. Marsden, Marc A. Wolman, Katharina E. Hayer, Jessica C. Nelson |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Reflex Startle Startle response Interneuron Hindbrain Stimulus (physiology) Biology Article General Biochemistry Genetics and Molecular Biology Fragile X Mental Retardation Protein 03 medical and health sciences 0302 clinical medicine Mauthner cell Interneurons Hypersensitivity medicine Animals lcsh:QH301-705.5 Cytoskeleton Zebrafish Adaptor Proteins Signal Transducing Behavior Animal medicine.diagnostic_test Excitatory Postsynaptic Potentials Zebrafish Proteins Axons 030104 developmental biology medicine.anatomical_structure Acoustic Stimulation lcsh:Biology (General) Mutagenesis Larva GCaMP CYFIP2 Calcium Neuroscience 030217 neurology & neurosurgery Genetic screen |
| Zdroj: | Cell Reports, Vol 23, Iss 3, Pp 878-887 (2018) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY 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. Graphical Abstract In Brief 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. |
| Databáze: | OpenAIRE |
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