Heterosis and resistance to DFP effects on spatial learning in C57BL X DBA hybrids

The inbred mouse strains C57BL/6Ibg and DBA/2Ibg differ in their ability to exhibit spatial learning in the Morris water task. C57BL mice learn the task well and show impairment of spatial learning following disruption of cholinergic function. DBA mice show rudimentary spatial learning ability, and are not further impaired when cholinergic function is decreased. These mice may carry genes regulating a noncholinergic spatial learning system. To test this hypothesis, first generation (F1) hybrids between DBA and C57BL mice were tested for spatial learning in the Morris water task. The hybrids performed better than either parental strain, suggesting that both parents contributed genes for spatial learning ability. Chronic treatment with diisopropylfluorophosphate (DFP), which abolished spatial learning ability in C57BL mice, produced only minor impairments in the hybrids. The behavioral resistance to DFP occurred despite significant reductions in hippocampal and cortical muscarinic binding. The results suggest either that the hybrids inherited a noncholinergic neurochemical system influencing spatial learning from their DBA parents or that the DFP treatment did not disrupt cholinergic function to a sufficient degree to impair the superior learning abilities of the F1 hybrids.