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FMRI and fcMRI phenotypes map the genomic effect of chromosome 13 in Brown Norway and Dahl salt-sensitive rats. Neuroimage 2014 Apr 15;90:403-12 PMID: 24084065

Pubmed ID

24084065

DOI

10.1016/j.neuroimage.2013.09.049

Abstract

Genes have been implicated as major contributors to many biological traits and susceptibility to specific diseases. However, the mechanisms of genotype action on central nervous system function have been elusive. It has been previously observed that inbred Brown Norway (BN) rats exhibit a number of quantitative complex traits markedly different from those of inbred Dahl salt-sensitive (SS) rats. These strains have become so important to cardiovascular research that a novel chromosome substitution approach was used to create SS and BN strains that have a single chromosome replaced by the homologous chromosome of the other strain. The present study was conducted in an effort to evaluate whether fMRI neuroimaging measures could be employed as a phenotype of genetic influence on neural biology in SS, BN, and consomic SSBN13 rat strains. Electrical forepaw stimulation evoked robust differential BOLD-fMRI activation along the thalamocortical pathway among the three strains across different stimulus frequencies. Moreover, using the fMRI-guided seeds in thalamus and somatosensory cortex for the analysis of fcMRI, we were able to characterize the strain-specific difference in secondary somatosensory cortex, temporal association cortex, and the CA3 region. We were also able to define the genetic influences of Chr-13 on the projection and integration of sensory information in consomic SS-13(BN) strain. We provided objective imaging evidence supporting the hypothesis that rat strain-specific fMRI and fcMRI combined with consomic strategy can be a useful tool in identifying the complex genetic divergence that is related to neural circuits. These findings prove the concept of neuroimaging-based phenotypes as a novel approach to visualize and fine-map the genetic effects onto brain biology at a systems level.

Author List

Li Z, Ward BD, Dwinell MR, Lombard JH, Pawela CP

Authors

Melinda R. Dwinell PhD Center Associate Director, Associate Professor in the Physiology department at Medical College of Wisconsin
Christopher Pawela PhD Assistant Professor in the Anesthesiology department at Medical College of Wisconsin




Scopus

2-s2.0-84893717855   1 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Brain
Brain Mapping
Chromosomes, Mammalian
Electric Stimulation
Magnetic Resonance Imaging
Male
Neural Pathways
Phenotype
Quantitative Trait Loci
Rats
Rats, Inbred BN
Rats, Inbred Dahl
jenkins-FCD Prod-331 a335b1a6d1e9c32173c9534e6f6ff51494143916