Early damage to the limbic system (amygdalohippocampal complex) in primates results in a severe and global loss of cognitive memory, though specific learning skill abilities are spared. This profound cognitive deficit is accompanied by emotional and social abnormalities resembling strikingly to those seen in autistic children. In short, these previous findings suggest that damage to the limbic system might have severe consequences on the development of cognitive and socioemotional behavior in primates. The present proposal is aimed at following these earlier findings in defining whether damage to the entire limbic system is necessary to produce the full-fledged syndrome or whether the syndrome can result from damage to specific parts of this complex. For this purpose, a group of investigators with special expertise in primate behavior, neuroendocrinology, neuroanatomy, and neurochemistry is assembled in the proposal to investigate the long-term consequences of neonatal damage to either the amygdaloid complex or the hippocampal formation on the development of (1) cognitive functions, (2) emotional behavior. (3) neuroendocrinological functions. and (4) brain morphological and neurochemical reorganization. The animals are already available and their cognitive and socioemotional behavior has been assessed by the P.I. when they were infants and juveniles. The present proposal is to determine the long-term consequences of these early selective limbic lesions by retesting the same animals as they have reached adulthood. The behavioral investigation will include a battery of behavioral tasks to assess a wide range of cognitive functions, emotional reactions, and food preference that will define specifically the functions that are lost vs those that are spared. The neuroendocrinological functions will be evaluated by modem endocrinological techniques and the reorganization of the brain will be studied by specific morphological and cytoimmunochemistry procedures. This research will provide the first comprehensive evaluation of the behavioral development of monkeys with neonatal restricted lesions of the limbic system and will permit direct correlations between behavioral changes with modifications of neuroendocrinological functions and specific reorganization of brain morphology and transmitter-specific systems. In addition, It will provide (1) experimental models of extreme value to elucidate the pathological bases of several developmental disorders such as autism, schizophrenia, and learning disabilities and (2) a point of departure for many future research aimed at the search for the causes of the limbic system neuropathology in developmental disorders as well as a search for possible treatment. Finally, the behavioral tasks used in the present proposal to assess cognitive functions in primates with specific limbic lesions can be directly standardized to develop non-invasive markers for assessing limbic system insult and integrity during the first years of life in human infants.
