Optical Tomography of Multiple Parallel Memory Systems in Freely Moving Rats

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DESCRIPTION (provided by applicant): It has been known for more than 50 years that experience-based changes in behavior (i.e., learning) and the mechanisms that store such changes come in at least two forms, one based in the hippocampus (a structure damaged in Alzheimer's Disease) and one outside the hippocampus. More recently, it has become clear that there are multiple memory areas, including the hippocampus, amygdala and striatum, which act in parallel, sometimes in cooperation, sometimes in competition, to control behavior. Modern imaging methods, including fMRI and PET scanning, have shown that this multiple memory system concept applies to humans as well as to other mammalian species, and have revealed important aspects of memory organization as learning proceeds. Unfortunately, the fMRI and PET methods are extremely expensive and, moreover, can be used only in immobilized or anesthetized subjects. Accordingly, our research plan is to use a novel, optical tomographic model to detect changes in memory structures in the course of learning by freely moving rats. This "diffuse optical tomography" (DOT) method permits us to look at the same hemodynamic variables measured by fMRI. Because we can detect oxy- and well as deoxy-hemoglobin by using 2 wavelengths, we can see aspects of the hemodynamic brain state not possible with current fMRI methods. We intend to use these capabilities in parallel with EEC recordings to look for changes that are expected to occur in three different memory areas while rats learn three different tasks. Prior lesion studies lead us to expect that the hippocampus will be preferentially activated in one task, the amygdala in a second, and the dorsal striatum in the third. A successful outcome to this promising work will constitute the beginning of a new study area that combines tomographic imaging in awake, freely moving animals with experimental methods impossible with humans. We anticipate that the proposed work will be of direct use in the analysis of pathological brain states and will in short order be applied to animal models of epilepsy, Alzheimer's Disease and other impairments of the nervous system.