DEVELOPMENT OF REVERSIBLE INACTIVATION TECHNIQUE STUDY HIGHER COGNITIVE FUNCTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In our studies we used state-of-the-art reversible inactivation techniques to probe in greater detail the interactions between different components of the medial temporal lobe in memory functions in monkeys. These methods permit individual structures within the medial temporal lobe to be selectively turned "off" and "on" for a short period of time while some specific memory functions are tested. These reversible inactivation procedures create "virtual lesions" as the underlying neural circuitry is not structurally disrupted and a particular site is only temporarily deactivated. In the current year, one adult male monkey received a presurgical MRI scan of the brain to determine the coordinate sites for our targeted structures (the hippocampi). Then, surgical implantation of two guide cannulae positioned at the anterior and posterior portions of each hippocampus and secured on the bone. This animal is currently behaviorally trained to measure spatial memory abilities. In half of the testing sessions the target structure is inactivated with muscimol (GABA agonist), and with the other half, vehicle is injected. Therefore each animal is used as its own control. The preliminary data indicate that muscimol achieved maximal behavioral effect between 25 minutes to one hour, after which the effects begin to wear off.