Early dysfunction of medial temporal lobe (MTL) structures is associated with many developmental mental disorders in humans, such as schizophrenia, autism, Williams syndrome. These disorders of unknown origin have significant impact on the normal cognitive development of a young individual, resulting in severe disabilities in the realms of perception, memory, language, thinking, experience of emotions, and social intelligence that span the entire life of an individual. Given the paucity of information in primates, regarding the normal anatomical and functional maturation of MTL structures and the long-term consequences of early damage to this region, the goal of our research program is to follow the anatomical and functional development of specific structures within this region, and compare and contrast the long-term behavioral and neuroanatomical effects of early vs late damage to this region. The overall hypothesis to be tested is whether early damage to the medial temporal lobe region yields the same behavioral changes, and anatomical and chemical re-organization than those seen after similar damage in adulthood.
The specific aims of the present application are (1) to continue our investigation of the role of hippocampal formation (HF) and perirhinal cortex (PRh) in the development of memory processes, (2) to compare and contrast the effects of early damage to these 2 structures on behavioral responses and cognitive processes, such as memory, emotional reactivity, social skills, and reward assessment, and (3) to study the anatomical and chemical re-organization of brain connections that follows the early hippocampal and perirhinal lesions. These behavioral studies will be performed in infant monkeys with neonatal selective HF and PRh lesions, and controls tested in behavioral tasks designed to measure memory, emotions, and social skills. These studies will provide insights into the pathophysiology and etiology of devastating developmental human disorders and primate model of extreme value for the development of new therapies.
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