The long term goal of this proposal is to determine the different contributions of the hippocampus and rhinal cortex in two types of functions: spatial location, and memory. While it is possible that the primate hippocampus provides the substrate for both functions, this has not been unequivocally demonstrated, in part because of technical difficulties in providing a test battery that evaluates both hypotheses. The present proposal is designed to evaluate these two broad views through the development of a novel behavioral paradigm- recordings of neuronal activity in freely moving monkeys. The use of freely moving monkeys will eliminate differences in the experimental approaches used to examine the functions of medial temporal structures in rats, monkeys, and humans; specifically by monitoring neuronal activity as monkeys perform tasks of learning and memory (thus enabling a comparison between monkeys and humans), as well as during locomotion around a complex spatial environment (thus enabling a comparison between monkeys and rats). In addition, we have utilized new techniques for collecting data: fine wire recording electrodes that remain in the brain for period of weeks; and multichannel technologies that allow us to obtain data on populations of neurons simultaneously. The proposed experiments will test fundamental and, in some instances, competing beliefs about the hippocampus. The specific objectives of this proposal are severalfold: 1. To compare the activity of hippocampal and rhinal cortical neurons in freely moving monkeys, and to dissociate neural mechanisms underlying the analysis of spatial location, from mechanisms underlying memorization and recall 2. Monkeys will be trained in a search task in which they simply walk to one of eight different locations within a complex spatial environment. Searching behavior results in the appearance of 'place cell' activity in rats, and so tests the hypothesis that spatial location is a relevant parameter for the primate hippocampus. Memory is irrelevant for the performance of this task. 3. Monkeys will be trained in versions of working memory tasks that require the retention of information about objects over delays of 5 seconds to 10 minutes. Hippocampectomized monkeys are impaired in these tasks, and so these test the hypothesis that memorization and recall are mediated by hippocampus and rhinal cortex. Spatial location is irrelevant for the performance of these tasks. 4. Monkeys will perform analogs of the 'spatial' and 'memory' tasks during complete immobilization. These tests will probe the importance of spatial location and locomotion, and allow comparison of neuronal activity in freely moving and restrained monkeys. These experiments should provide a functional perspective on the role of the hippocampus in memory and elucidate the consequences of hippocampal ablation in the treatment of medial temporal lobe disease.
