Cognitive performance is highly sensitive to prior experience in mice with a learning and memory deficit: Failure leads to more failure

The impact of a previously successful or unsuccessful experience on thesubsequent acquisition of a related task is not well understood. The nature ofpast experience may have even greater impact in individuals with learningdeficits, as their cognitive processes can be easily disrupted. Mice with atargeted disruption of the α and δ isoforms of the cAMP-responseelement-binding protein (CREB) gene (CREB αδ- -deficientmice) have a genetic vulnerability to impaired learning and memory that ishighly influenced by experimental conditions. Thus, we studied the impact ofprior successful and unsuccessful experiences on the degree to whichCREB αδ- -deficient mice exhibit impaired spatiallearning and memory in the Morris water maze (MWM). In Experiment 1, wereplicated the cognitive deficit of CREB αδ- -deficientmice when given two trials per day with a 1-min intertrial interval (MWM2),and labeled this experience as a “failure.” We rescued the deficitusing four trials per day with a 3- to 5-min intertrial interval (MWM4) andlabeled this experience a “success.” In Experiment 2, a new, naiveset of wild-type (WT) and CREB αδ- -deficient mice wererandomly assigned to one of two sequence protocols to assess the influence ofa success or a failure on subsequent performance. In Group 1, mice were firstexposed to the MWM4 condition, followed by the more difficult MWM2 task. Asexpected, CREB αδ- -deficient mice performed well in theMWM4; they also performed well during reversal testing (MWM4R) where the goallocation is changed. With this initial successful learning experience, theCREB αδ- -deficient mice then performed as well as WTmice in the MWM2, the condition in which they are known to be impaired. Incontrast, CREB αδ- -deficient mice in Group 2 had anunsuccessful experience when first exposed to the MWM2 condition, and thenalso showed impairment in the MWM4, the condition in which they would normallyperform well. This deficit was amplified whenCREB αδ- -deficient mice were then tested in the reversaltest. Sex differences in learning amongCREB αδ- -deficient mice were amplified upon exposure toan unsuccessful learning experience. These data indicate that, underconditions of cognitive impairment, past experience can—depending on itsnature—significantly facilitate or hinder future performance.