Memory may be conceptualized into three phases of information manipulation: those processes that handle the encoding of, storage of, and drawing upon learned and witnessed facts and events, which for humans is encoded physiologically. Two general forms of memory have been classified according to their duration in time: short-term memory (STM), which is rapidly formed and can outlast training from minutes to hours, and long-term memory (LTM), which lasts from hours to days, weeks, or even years.2) The hippocampus is a brain structure that plays a critical role in learning and memory in humans and animals.3) There have been many trials to find memory enhancing or cognition enhancing agents to ameliorate dementia. 8) Other studies report that YMJ increases neurogenesis in the dentate gyrus of the hippocampus in stressed rats 9) while enhancing memory retention and cognitive activities related to memory processes. 7,8) It is also reported that YMJ reverses scopolamine-induced and p-chloroamphetamine-induced amnesia in rats. 7) In addition, our unpublished data shows that YMJ derivatives (YMJd), including Lycii fructus, enhance memory retention by protecting neuronal cells from attack by reactive oxygen species (data not shown). In our recent study, K-WAIS, the Korean version of the WAIS test, and Event-Related Potential P300 latency during auditory oddball tasks were measured to assess the effect of YMJd on cognitive abilities in normal human subjects before and after 6 weeks of YMJd treatment. We found that the K-WAIS mean scores of the group treated with YMJd were significantly higher than those of the placebo group (pϽ0.05), while their mean P300 latency was substantially shorter (pϽ0.005). These results suggest that YMJd treatment accelerates the speed of information processing and enhances cognitive ability. 10) Thus, those results suggest that YMJ and its derivatives may be useful agents for the enhancement of learning and memory. However, there have been few reported studies on accessing the mechanism of memory enhancement triggered by treatment with YMJ or YMJd. The present study is designed to evaluate the action and mechanism behind the memory-enhancing effect of the herbal extract YMJd. Our results revealed that YMJd has a significant effect on memory enhancement and the expression of genes associated not only with the prevention of neuronal degeneration but also with neuronal growth events. The herbal extract Yukmijihwang-tang (YMJ) has been widely used for centuries as an anti-aging herbal medicine in Asian countries. Among the various modified prescriptions of YMJ, YMJ derivatives (YMJd) were formulated to enhance memory retention. This study has three goals: 1) to quantitatively evaluate the memoryenhancing effect of YMJd using behavior tasks; 2) to use cDNA micro-array tools to identify candidate genes responsible for enhancing memory; and 3) to statistically evaluate the specific gene expression patterns using Real-time PCR. Memory retention abilities are addressed by the passive avoidance task with...