We have shown previously that feeding dietary cholesterol before learning can improve acquisition whereas feeding cholesterol after learning can degrade long term memory. To examine these different findings within a single paradigm, we fed groups of rabbits 2% cholesterol or normal chow with or without 0.12 ppm copper added to the drinking water following two-tone discrimination learning of the nictitating membrane response in which a 8-kHz tone (conditioned stimulus, CS+) was followed by air puff and a 1-kHz tone (CS-) was not. After eight weeks on the diet, we assessed the rabbits' conditioned responding during testing and retraining. We then reversed the two-tone discrimination and assessed responding to the 1-kHz tone CS+ and the 8-kHz CS-. During testing, rabbits given cholesterol without copper had lower levels of responding to CS+ than rabbits in the other groups suggesting they did not retain the discrimination as well. However, during a brief discrimination retraining session, their response levels to the CS+ returned to the level of the other groups, demonstrating a return of the memory of the original discrimination. At the end of discrimination reversal, these same rabbits exhibited superior discrimination indexed by lower response levels to CS- but similar levels to CS+, suggesting they were better able to acquire the new relationship between the two tones by inhibiting CS- responses. These results add to our previous data by showing cholesterol diet-induced degradation of an old memory and facilitation of a new memory can both be demonstrated within a discrimination reversal paradigm. Given discrimination reversal is a hippocampally-dependent form of learning, the data support the role of cholesterol in modifying hippocampal function as we have shown previously with in vitro brain slice recordings.
Acoustic Stimulation Animals