Normal memory depends on a system of anatomically related structures in the medial temporal lobe that includes the hippocampal formation and perirhinal cortex. Damage to these structures causes profound impairment in the ability to establish a reliable record of the events and episodes that comprise our lives. The specific information processing functions that enable episodic memory are poorly understood, however, and there is no consensus on how the hippocampus and related brain regions contribute this capacity. The perspective developed in the present application is that advances in neurological research and cognitive psychology converge on a valuable strategy for defining the brain organization of memory in primates. In one set of experiments, intact monkeys and animals with selective ibotenic acid lesions of the hippocampus (the dentate gyrus, hippocampus proper, and subiculum) will be tested across a battery of assessments designed to manipulate demands on candidate operating characteristics of episodic memory: l) the temporal organization of memory, 2) memory for context, 3) """"""""autobiographical"""""""" memory, and 4) the relational organization of memory. Although a variety of tasks are proposed, the underlying strategy involves a novel approach to cognitive assessment that uses carefully designed probe tests to go beyond standard accuracy measures, illuminating the representational structure of normal an disordered memory. By this design the overall aim is to define the information processing functions of the primate hippocampus that enable episodic memory. A second set of experiments targets a closely related goal. One perspective on the organization of the medial temporal lobe is that the hippocampus and perirhinal cortex operate as a functional unit, subserving overlapping and redundant processing capacities in support of memory. Other evidence suggests a different conclusion, that the structures comprising this system are functionally specialized. These alternatives will be evaluated in the proposed project by comparing the cognitive effects of damage to the hippocampus with selective aspiration lesions of the perirhinal cortex (Areas 35 and 36). Using the same extensive battery of assessments across investigations, the overall goal is to test the hypothesis that the hippocampus and perirhinal cortex mediate qualitatively distinct mnemonic processing functions. Taken together, the results will substantially illuminate the structure and organization of memory in the primate brain and, ultimately, fuel progress in research on a variety of clinical conditions in which the medial temporal lobe an memory are prominently affected.
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| Shamy, J L; Carpenter, D M; Fong, S G et al. (2010) Alterations of white matter tracts following neurotoxic hippocampal lesions in macaque monkeys: a diffusion tensor imaging study. Hippocampus 20:906-10 |
| Shamy, Jul Lea; Buckmaster, Cindy A; Amaral, David G et al. (2007) Reactive plasticity in the dentate gyrus following bilateral entorhinal cortex lesions in cynomolgus monkeys. J Comp Neurol 502:192-201 |
| Buckmaster, Cindy A; Eichenbaum, Howard; Amaral, David G et al. (2004) Entorhinal cortex lesions disrupt the relational organization of memory in monkeys. J Neurosci 24:9811-25 |
