Could Memory Performance and Spatial Learning Be Genetically Based?

New study provides evidence for independent genetic determinants in two cognitive functions

(February 4, 2004) – BETHESDA, MD – As the US population ages, there is an increasing effort to understand the underlying mechanisms that contribute to learning and memory. This effort could be of critical importance to scientists trying to decipher how the molecular genetic mechanisms of learning and memory are disrupted or impaired. The results of a new study provide evidence that individual differences in some cognitive functions may have a genetic basis.

A New Study

The authors of the study are Nelson Ruiz-Opazo, of the Section of Molecular Medicine, Boston University School of Medicine, Boston, MA, and John Tonkiss, from the Center for Behavioral Development and Mental Retardation, Boston University School of Medicine, Boston, MA. Their study, entitled “X-Linked Loci Influence Spatial Navigation Performance in Dahl Rats,” now appears in the Articles in Press section of Physiological Genomics, one of one of 14 scientific journals published monthly by the American Physiological Society (APS) (www.the-aps.org).

Methodology

Dahl S/hsd (n=12) and Dahl R/hsd (n=12) male rats were obtained. Reciprocal mating of the parental strains (Dahl R female x Dahl S male and Dahl S female x Dahl R male) produced two types of F1 male hybrids: F1[RXS] (n=12) and F1[SXR] (n=11), respectively. A cohort was derived from brother-to-sister mating of F1 (R female x S male) hybrids to produce and F2 male segregation population (n=178). Behavioral testing was performed on parental, F1 and F2 cohorts at 12 weeks of age.

The Morris water maze (MWM) task was performed using a circular water maze and a computer tracking system. A circular platform was placed at the center of one of four imaginary quadrants and the water rendered opaque. Swim distance was used to evaluate performance.

• In the hidden platform version of the maze task the platform was submerged below the water’s surface and 12 swim trials were given per day over two consecutive days. Animals were placed into the maze at one of three randomized starting points and allowed to traverse the maze in search of the escape platform. On each trial, a maximum of 60 seconds of swim time was allowed. Between trials, a 35 second interval was imposed with the rat on the platform. At the end of the 24^th trial, the platform was removed (probe trial) and the animal was allowed to search for one minute. The distance traveled in the target quadrant [T] and the three other quadrants adjacent-left [A_L], adjacent-right [A_R], and opposite[O] was expressed as a percentage of the total distance traveled.   

• In the visible platform version all visual cues were removed from the room, the platform was raised 2 cm above the surface of the water and two 15 cm high dark cylinders were attached to it. Twelve consecutive trials were then administered with a 35 second inter-trial interval, as above. The platform was moved in a random fashion between each trial.

Genotyping (the “blueprint” or set of instructions for building and maintaining a live creature) was done with six chromosome X markers. Quantitative trait locus (QTL; the combined influences of numerous genes) analysis was performed using the cumulative distance traveled over the 24 trials as the index of acquisition performance (ACQ^TD). The percent of distance traveled on the probe trial was used as the index of spatial accuracy (SpA).  Linkage map, marker regression and interval mapping analyses were done to generate a likelihood ratio statistic as a measure of the significance of a possible QTL. A backcross analytic design was used to perform both the permutation test as well as the QTL analysis. Genetic distances were calculated with a Kosambi mapping function, and critical significance values for interval mapping were determined by a permutation test.

Two-Way Repeated Measures ANOVA, one-way ANOVA or t-tests (when indicated) were used to analyze behavioral data. All statistical tests were two-tailed and differences were considered significant at the P<0.05 level. 

Results

The researchers found that:

• 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 for the impairment in the spatial navigation observed in the Dahl S rats;

• QTL analysis of an (RXS) F2 male population phenotyped for spatial  navigation detected two QTLs on chromosome X as influencing spatial navigation performance; and 

• One QTL (Nav-1, centered at DXRat21, significant for linkage) influenced the acquisition performance without affecting spatial accuracy performance. The second QTL (Nav-2, centered at DXRat25, significant for linkage) affected the spatial accuracy performance with no detectable effect on acquisition performance. 

Conclusions

These results provide evidence for the existence of independent genetic determinants for of different aspects of spatial learning and memory performance. Clearly, new insights into the genetic mechanisms underlying the cognitive function can be gleaned from such analysis and the Dahl rat appears to provide a powerful model to accomplish those goals.

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Source: Articles in Press section of the journal Physiological Genomics.

The American Physiological Society (APS) was founded in 1887 to foster basic and applied science, much of it relating to human health. The Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals every year.

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Editor’s Note: A copy of the research article is available in pdf format to the press.

Members of the press are invited to obtain a pdf copy of the study and to interview members of the research team. To do so, please contact Donna Krupa at 703.527.7357 (direct dial), 703.967.2751 (cell) or djkrupa1@aol.com.