The hippocampus is critical to what is termed declarative memory, our ability to consciously recall the events of our lives and to connect us with our past. It is also vulnerable to the deleterious effects of Alzheimer's dementia, stress, alcohol, stroke and other brain insults. Thus, this region of the brain continues to be a major target for gaining insights into the biological basis of memory that could lead to treatments, which could benefit people with memory disorders. The proposed research focuses on the hippocampus and to a lesser extend its interactions with the amygdala, with the goal of advancing our basic understanding of memory processes.
Our specific aims are directed at three issues.
In Aim 1 we will determine the contributions gluatamate receptors (NMDA and AMPA) in the hippocampus and amygdala make to the mnemonic and non-mnemonic functions of these regions by studying their roles in contextual fear conditioning and memory for context.
In Aim 2 we will study memory maintenance processes that may be important for stabilizing hippocampal-dependent memories. This work is based on recent findings that for several days following a learning experience the resulting memory are vulnerable to disruption. These studies will investigate the hypothesis that glutamate receptor activation is critical to memory maintenance.
In Aim 3 we focus on hippocampal dependent memories to investigate a novel hypothesis about the function of certain immediate early genes (lEGs), specifically, that one function of lEGs is to prime the memory system to facilitate the storage of subsequent events. It has two components: (a) experience at time 1 can influence the storage of a subsequent event experienced at time 2 and (b) this effect is mediated by lEGs. We propose experiments to test the implications of both components. This work will contribute to a more complete understanding of the basic mechanisms that support declarative memory and indirectly to the development of treatments to ameliorate memory disorders. ? ?
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