The primary purpose of the present proposal is to test whether there is a correspondence between animals and humans in terms of prefrontal cortex mediation of memory function and to determine whether specific sub-regions of the prefrontal cortex (e.g., medial precentral, anterior cingulate, infralimbic and prelimbic, dorsolateral frontal or lateral precentral, agranular insular, and ventromedial orbital cortex) differentially mediate specific working memory functions for different attributes as well as mediate higher- order relationships based on temporal ordering of information and paired associate learning. Previous research in rats with prefrontal cortex lesions has suggested that rats also have difficulty in working memory for different attributes, difficulty in temporal ordering of specific attribute information, difficulty in learning and retention of paired associate attribute information and furthermore that different sub- regions may mediate these attributes. In order to elaborate further on the role of different sub-regions of the prefrontal cortex in mediating working memory, Dr. Kesner has developed a set of behavioral tasks in which one can measure: a) not only working memory for spatial location, as defined by an object in a specific location, but also working memory for allocentric spatial distance (distance between 2 objects) and egocentric spatial distance (distance between subject and object) as well as working memory for visual objects independent of spatial location, b) working memory for an egocentric spatial (motor, right-left turn response) c) working memory for affect as measured by magnitude of reinforcement, d) a lag function for memory for order information not only for a list of spatial locations, but also for a list of visual objects, e) learning and performance of object- object, object-spatial location and spatial location-spatial location paired associate information. Dr. Kesner proposes to use this animal model as a means of continuing the investigation of the role of the prefrontal cortex in mediating working memory for specific attribute information and higher- order mnemonic processes such as temporal order and paired associate learning.
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