The long-term objective of this research is to provide a clearer understanding of the functioning of the medial temporal lobe memory system by using reversible cooling lesions of the hippocampus. This is a particularly important health related issue because this region of the brain is critically important for memory, yet is vulnerable to damage in various pathological conditions, including those associated with stroke, aging, and Alzheimer's disease. We propose to use reversible cooling lesions during the delayed nonmatching to sample task in the monkey model of human medical temporal lobe amnesia.
The specific aims related to the proposed studies are, 1) to adapt the miniature cooling probe technology to work with monkeys, 2) replicate the permanent lesions studies of the hippocampus using cooling lesions, 3) assess hippocampal function during information encoding, storage and retrieval, and 4) determine if there is a relationship between extent of hippocampal disruption and severity of memory disruption.
These aims will be accomplished by implanting 6 cooling probes (3 on each side of the brain) along the rostrocaudal extent of the hippocampus. The exact placements will be determined by magnetic resonance images of each monkey's brain. Monkeys will be trained on the delayed nonmatching to sample task and tested at 1 second and 10 minute delays. The hippocampus will be inactivated at various phases of the task (stimulus presentation, delay interval, and retrieval testing) to determine how critical hippocampal functioning is on information encoding, storage and retrieval, and if increasing the area of disruption increases the magnitude of the memory impairment.
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| Clark, R E; Gohl, E B; Lavond, D G (1997) The learning-related activity that develops in the pontine nuclei during classical eye-blink conditioning is dependent on the interpositus nucleus. Learn Mem 3:532-44 |
| Clark, R E; Zhang, A A; Lavond, D G (1997) The importance of cerebellar cortex and facial nucleus in acquisition and retention of eyeblink/NM conditioning: evidence for critical unilateral regulation of the conditioned response. Neurobiol Learn Mem 67:96-111 |
