The proposed research will employ focal intracerebral microinfusions of drugs stereotaxically directed at specific regions of the medial temporal lobe: perirhinal piriform cortex, entorhinal cortex, parahippocampal gyrus, and amygdala. These microinfusions will be administered to awake, behaving monkeys via chronically indwelling cappulas, immediately prior to evaluating performance on a visual recognition memory task. The drugs to be used for the intracerebral infusions are selected for their effects on specific amino acid neurotransmitter receptors: 1) drugs which block excitatory transmission mediated via glutamate receptors (NMDA and non-NMDA subtypes) and 2) drugs which enhance inhibitory transmission mediated via GABAA receptors. The brain regions to be investigated have been selected on the basis of studies in the literature which have demonstrated significant deficits in visual recognition memory following individual or conjoint lesions of those regions. In the experiments proposed, each subject will be repeatedly tested under drug and control conditions so that each subject serves as its own control and different drugs and infusions into various brain areas can be compared within the same subject. Once one or more brain areas (alone or in combination) have been identified in which the drug treatments impair performance on the recognition memory task, the anatomic site-specificity of the drug effect will be evaluated. It is expected that blockade of excitatory transmission in perirhinal and entorhinal cortex, as accomplished by the focal application of glutamate antagonists in GABA agonists, will rapidly and reversibly impair performance on a visual recognition memory task. Furthermore, it is expected that this acute impairment will require only unilateral drug application, in contrast to the bilateral damage required in chronic ablation studies. It is hoped that the results of these studies will: (1) provide the basis for a more detailed investigation of the neurochemical and neuroanatomic substrates of memory functions subserved by neural networks in the limbic cortex; and (2) provoke additional studies in the nonhuman primate using focally applied chemical agents to probe brain regions crucial for cognitive function. The use of reversibility-acting intracerebral focal drug infusions is expected to offer several advantages in studying the role of specific brain regions for memory functions in non-human primates. In particular, a) the ability to use each subject as its own control reduces experimental variability and decreases the number of monkeys needed to generate interpretable data; b) the ability to test the same subject repeatedly using different drugs or different anatomical sites of infusion, maximizes the amount of experimental data that can be generated from a single monkey and increases the anatomical resolution that can be obtained; c) the ability to avoid damage to fibers of passage and problems with secondary degeneration which complicate the interpretation of lesion studies; and d) the ability to avoid permanent damage to the monkeys allows for non-terminal experiments in which the animals can be used subsequently for other studies. These advantages could greatly enhance the feasibility and utility of pursuing this important field of research in monkeys. The project furthers VPW program objectives to provide opportunities for women to advance their careers in science or engineering through research, and to encourage other women to pursue careers in these areas through the investigator's enhanced visibility as a role model on the host campus. The proposed activities which contribute to the second objective include: training and mentoring graduate and undergraduate students by involving them in the experiments proposed; teaching a graduate elective course in Psychology (also open to undergraduates); leading a workshop for Women in Science through the Department of Women's Studies; presenting research accomplishments in lectures/colloquia sponsored by the Psychology Department and also in a forum sponsored by the Northwest Center for Research on Women; regularly attending student-faculty journal clubs in the Psychology Department, as well as weekly Student Research Seminars in physiological psychology.
