Newly acquired information becomes long-term memory through a process known as consolidation, which depends on an initial phase of gene transcription and translation. Stress and glucocorticoid hormones, which are released into the circulation following stressful experiences have been shown to significantly modulate memory consolidation in humans and animal models. Consistent with the hypothesis that glucocortocoid hormones can modulate memory consolidation, glucocorticoid receptors (GR) are expressed at high levels in brain regions that are known to be necessary for memory consolidation, such as the hippocampus and the amygdala. Although a great deal is known about the neural substrates mediating the behavioral effects of glucocorticoids, the underlying molecular mechanism remains be investigated. The immediate goal of this proposal is to investigate the involvement of genes that are known to be critical for memory consolidation, such as pCREB, C/EBP ? and d, and BDNF, in glucocorticoid receptor-dependent memory modulation in the hippocampus. Specifically, expression levels and/or DNA binding activities of pCREB, C/EBP ?, C/EBP d and BDNF will be measured after training and GR activation or inhibition using quantitative western blot, RT-PCR and/or EMSA. Another aspect of this proposal aims to investigate the relationship between hippocampal GR and C/EBP ?, C/EBP d and BDNF at the cellular levels. Expression levels and localization of these genes will be analyzed in hippocampal neuronal cultures following GR activation. More broadly, since very little is known about how the glucocorticoid hormones modulate memory consolidation, this proposal aims to broaden our molecular and cellular understanding of glucocorticoid receptor-dependent memory modulation. The results from this proposal will further our understanding of the nature and the function of the stress and GR-dependent memory consolidation. They will also be helpful for the development of treatment of several stress and memory related pathologies, including Post-Traumatic Stress Disorder (PTSD) and depression.