PUBLICATION
cacna2d3, a voltage-gated calcium channel subunit, functions in vertebrate habituation learning and the startle sensitivity threshold
- Authors
- Santistevan, N.J., Nelson, J.C., Ortiz, E.A., Miller, A.H., Kenj Halabi, D., Sippl, Z.A., Granato, M., Grinblat, Y.
- ID
- ZDB-PUB-220715-8
- Date
- 2022
- Source
- PLoS One 17: e0270903 (Journal)
- Registered Authors
- Granato, Michael, Grinblat, Yevgenya
- Keywords
- none
- MeSH Terms
-
- Habituation, Psychophysiologic*/genetics
- Reflex, Startle*/genetics
- Larva/genetics
- Learning/physiology
- Animals
- Zebrafish*/genetics
- Acoustic Stimulation
- Calcium Channels*/genetics
- PubMed
- 35834485 Full text @ PLoS One
Citation
Santistevan, N.J., Nelson, J.C., Ortiz, E.A., Miller, A.H., Kenj Halabi, D., Sippl, Z.A., Granato, M., Grinblat, Y. (2022) cacna2d3, a voltage-gated calcium channel subunit, functions in vertebrate habituation learning and the startle sensitivity threshold. PLoS One. 17:e0270903.
Abstract
Background The ability to filter sensory information into relevant versus irrelevant stimuli is a fundamental, conserved property of the central nervous system and is accomplished in part through habituation learning. Synaptic plasticity that underlies habituation learning has been described at the cellular level, yet the genetic regulators of this plasticity remain poorly understood, as do circuits that mediate sensory filtering.
Methods To identify genes critical for plasticity, a forward genetic screen for zebrafish genes that mediate habituation learning was performed, which identified a mutant allele, doryp177, that caused reduced habituation of the acoustic startle response. In this study, we combine whole-genome sequencing with behavioral analyses to characterize and identify the gene affected in doryp177 mutants.
Results Whole-genome sequencing identified the calcium voltage-gated channel auxiliary subunit alpha-2/delta-3 (cacna2d3) as a candidate gene affected in doryp177 mutants. Behavioral characterization of larvae homozygous for two additional, independently derived mutant alleles of cacna2d3, together with failure of these alleles to complement doryp177, confirmed a critical role for cacna2d3 in habituation learning. Notably, detailed analyses of the acoustic response in mutant larvae also revealed increased startle sensitivity to acoustic stimuli, suggesting a broader role for cacna2d3 in controlling innate response thresholds to acoustic stimuli.
Conclusions Taken together, our data demonstrate a critical role for cacna2d3 in sensory filtering, a process that is disrupted in human CNS disorders, e.g. ADHD, schizophrenia, and autism.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping