Memory and Hippocampus: Anaylsis of Retrograde Amnesia

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Robert E. Clark, Ph.D.NSF Proposal Number: 0237053NSF Proposal Title: Memory and Hippocampus: Analysis of Retrograde AmnesiaA considerable body of work has been directed toward understanding how a brain structure known as the hippocampus contributes to memory function. A phenomenon that has been especially important to this tradition of work is temporally-graded retrograde amnesia (TGRA). TGRA refers to the finding that information (memories) learned long before the onset of memory impairment are often spared relative to information learned more recently. For example, humans who have sustained damage to the hippocampus, have little or no memory for facts and events that was learned just prior to their brain damage, but retain memories that were learned well before the damage. Accordingly, memory that is initially hippocampus-dependent, gradually becomes hippocampus-independent. A critical question is how hippocampal activity participates in this process.These experiments provide a systematic investigation of when and for how long the hippocampus must be active to support memory. Using rats, reversible lesions will be used to selectively inactivate the hippocampus (by infusing a drug that disrupts hippocampal function without damaging the neurons). Accordingly, the hippocampus can be turned on or off during different phases of the learning and memory process. That is, reversible lesions will be applied during different portions of the learning, retention, or retrieval phase of memory to determine if and when hippocampal activity is important for memory. These reversible lesions are created and sustained for long periods of time with implanted osmotic minipumps (devices that can slowly deliver the drugs to the hippocampus continuously for many days). These results will provide important insights into how hippocampal activity following learning contributes to the establishment of long-term memory. Clarifying this pattern of memory loss (TGRA) is critical for understanding how memory is organized and stored in the brain. The proposed activities will provide research training for graduate students and post-doctoral students in psychology, cognitive science, and neuroscience.