Hereditary covariations of neuronal circuitry and behavior: Correlations between the proportions of hippocampal synaptic fields in the regio inferior and two-way avoidance in mice and rats

Abstract

By means of Timm's silver sulfide stain, the proportions of synaptic terminal fields covering cross-sections from the regio inferior of the hippocampus were determined planimetrically at a mid-septotemporal level. Analysis was performed in rats from two lines (6 RHA, 7 RLA) selectively bred for extremes in the acquisition of a two-way avoidance task, in 34 mice of 7 strains (DBA/2, BALB/c, NMRI, C57BL/6, SM/J, C3H, ICR) known for genetically dependent differential performance in two-way avoidance performance, and in 20 behaviorally tested mice from a stock systematically bred for randomization of its genotype. Results show that genetic selection for shuttle-box learning in rats led to differences in the proportions of ‘Timm-positive’ hippocampal terminal fields. In poor avoiders (RLA), the combined intra- and infrapyramidal mossy fiber projection covered a distinctly greater area than in RHA-rats ( P = 0.001). The hilar mossy fiber projection was larger in the RLA-rats ( P = 0.01), but the suprapyramidal projection was equal in both strains. In addition, RLA-rats had a comparatively smaller stratum oriens and stratum lacunosum-moleculare ( P = 0.05) as well as a tendency for a smaller regio inferior ( P = 0.074). In the inbred mouse strains, correlations between the means of known strain-specific avoidance scores and the means of strain-specific terminal fields showed, as in rats, a close negative association between the area occupied by mossy fiber terminals on the basal parts of hippocampal pyramidal neurons (intra- and infrapyramidal) and avoidance performance ( r = −0.90). No other significant correlations were observed. In the 20 mice tested individually, the anatomico-behavioral correlations were analyzed by multiple regression techniques. The proportion of the regio inferior occupied by the combined intra- and infrapyramidal mossy fiber projection was the only morphological variable in the regio inferior showing a significant partial regression with avoidance performance. Morphometric measures accounted for no less than 88% of the behavioral variation. We conclude: (1) rather subtle hereditary variations in hippocampal circuitry are closely related to variations in acquisition and performance of a particular avoidance learning task; and (2) the psychological variable which covaries positively with the intra- and infrapyramidal mossy fiber projection seems to be the persistence of inappropriate coping responses of mice and rats in the shuttle-box.