Investigation of visual memory in the nonhuman primate has enjoyed remarkable recent success, among other things, in demonstrating the closeness between human and nonhuman primate mnemonic processing and amnesias. This success has come largely from using the technique of destruction of relevant portions of the neuronal substrate, e.g., hippocampal formation. However, possibly because of limitations of lesioning technique, information on the time course of initial storage and retrieval occurring within the putative mnemonic circuitry is absent in this account. Experiments performed in this laboratory, during the previous support period, have now revealed a unique opportunity to address such questions with unexpected precision. It was found that a single electrical burst of one to four pulses lasting less than 50 milliseconds (ms), delivered to the hippocampal formation in macaques 50-200 ms after a 50 ms view of visual image, eliminates their ability to recognize that image subsequently. Such pulses before or after this period are essentially without effect. Similarly, delivery of electrical stimulation while the animal is endeavoring to retrieve a previously viewed image severely disrupts its accuracy. Such pulses are otherwise without effect upon performance. The proposed experiments then, will use brief perturbing pulses to measure the temporal course of mnemonic processing with great precision, and do so for different components of the hippocampal formation. to this end, advantage will be taken of the fact that performance by a single hemisphere in a split-brain macaque is essentially equivalent to that with both hemispheres; thus it will be possible to achieve the perturbation from a single locus at a time, greatly enhancing the ability to specify critical sites. The contribution of this project is aimed directly at the neuronal circuitry supporting memory. Its clinical relevance is not immediate but could nonetheless be profound since it would be rather surprising if a full understanding of the mnemonic circuitry did not have a major impact on the important - and with the aging population - growing health problems involving memory.
