RGD Reference Report - Robust and replicable measurement for prepulse inhibition of the acoustic startle response. - Rat Genome Database

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Robust and replicable measurement for prepulse inhibition of the acoustic startle response.

Authors: Miller, Eric A  Kastner, David B  Grzybowski, Michael N  Dwinell, Melinda R  Geurts, Aron M  Frank, Loren M 
Citation: Miller EA, etal., Mol Psychiatry. 2020 Mar 6. pii: 10.1038/s41380-020-0703-y. doi: 10.1038/s41380-020-0703-y.
RGD ID: 35668860
Pubmed: PMID:32144356   (View Abstract at PubMed)
PMCID: PMC7483293   (View Article at PubMed Central)
DOI: DOI:10.1038/s41380-020-0703-y   (Journal Full-text)

Measuring animal behavior in the context of experimental manipulation is critical for modeling, and understanding neuropsychiatric disease. Prepulse inhibition of the acoustic startle response (PPI) is a behavioral phenomenon studied extensively for this purpose, but the results of PPI studies are often inconsistent. As a result, the utility of this phenomenon remains uncertain. Here, we deconstruct the phenomenon of PPI and confirm several limitations of the methodology traditionally utilized to describe PPI, including that the underlying startle response has a non-Gaussian distribution, and that the traditional PPI metric changes with different stimuli. We then develop a novel model that reveals PPI to be a combination of the previously appreciated scaling of the startle response, as well as a scaling of sound processing. Using our model, we find no evidence for differences in PPI in a rat model of Fragile-X Syndrome (FXS) compared with wild-type controls. These results in the rat provide a reliable methodology that could be used to clarify inconsistent PPI results in mice and humans. In contrast, we find robust differences between wild-type male and female rats. Our model allows us to understand the nature of these differences, and we find that both the startle-scaling and sound-scaling components of PPI are a function of the baseline startle response. Males and females differ specifically in the startle-scaling, but not the sound-scaling, component of PPI. These findings establish a robust experimental and analytical approach that has the potential to provide a consistent biomarker of brain function.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Fmr1Ratabnormal prepulse inhibition no_associationIAGP compared to wild type controlsRGD 
Fmr1Ratabnormal prepulse inhibition sexual_dimorphism IAGP in wild type controlsRGD 
Fmr1em2McwiRatabnormal prepulse inhibition no_associationIAGP compared to wild type controlsRGD 
Fmr1em2McwiRatabnormal prepulse inhibition sexual_dimorphism IAGP in wild type controlsRGD 
LE-Fmr1em2McwiRatabnormal prepulse inhibition no_associationIAGP compared to wild type controlsRGD 
LE-Fmr1em2McwiRatabnormal prepulse inhibition sexual_dimorphism IAGP in wild type controlsRGD 
Fmr1Ratabnormal startle reflex no_associationIAGP compared to wild type controlsRGD 
Fmr1Ratabnormal startle reflex sexual_dimorphism IAGP in wild type controlsRGD 
Fmr1em2McwiRatabnormal startle reflex no_associationIAGP compared to wild type controlsRGD 
Fmr1em2McwiRatabnormal startle reflex sexual_dimorphism IAGP in wild type controlsRGD 
LE-Fmr1em2McwiRatabnormal startle reflex no_associationIAGP compared to wild type controlsRGD 
LE-Fmr1em2McwiRatabnormal startle reflex sexual_dimorphism IAGP in wild type controlsRGD 
Objects Annotated

Genes (Rattus norvegicus)
Fmr1  (fragile X messenger ribonucleoprotein 1)
Fmr1em2Mcwi  (FMRP translational regulator 1; CRISPR/Cas9 induced mutant 2, Medical College of Wisconsin)

Strains
LE-Fmr1em2Mcwi  (NA)


Additional Information