X-linked loci influence spatial navigation performance in Dahl rats.

Elucidation of natural genetic variations underlying strain or individual differences in cognitive function has remained elusive. Here we report the identification of two genetic loci that influence spatial navigation in Dahl rats. In the Morris water maze test, Dahl R rats exhibited efficient spatial navigation, whereas Dahl S rats displayed poor spatial navigation (accuracy). Analysis of F1 male progeny of reciprocal crosses between Dahl S and Dahl R strains implicated the X chromosome with the impairment in spatial navigation observed in Dahl S rats. Quantitative trait locus (QTL) analysis of an (RXS) F2 male population phenotyped for spatial navigation detected two QTLs on chromosome X influencing spatial navigation performance. One QTL (Nav-1, centered at DXRat21, significant for linkage) influenced acquisition performance without affecting spatial accuracy performance; and the second QTL (Nav-2, centered at DXRat25, significant for linkage) affected spatial accuracy performance with no detectable effect on acquisition performance. Our results demonstrate X linkage of spatial navigation performance in Dahl rats and provide evidence for the existence of independent genetic determinants for defined behavioral components of spatial navigation.