There is accumulating evidence that the prefrontal cortex is involved in working memory in several mammalian species. Prefrontal cortex damage leads to a variety of working memory deficits in humans, as well as rodents. These results suggest that the prefrontal cortex may be involved in working memory for different attributes, i.e. space, affect, motor responses. Recent evidence suggest that the type of working memory deficit that results following prefrontal cortex damaged may be related to the lesion site. Understanding whether specific prefrontal cortex subregions mediate different types of information within a working memory context, will lend important insight into the biology of memory. To build a more comprehensive view of the neural processes that underlie memory within prefrontal cortex subregions, also calls for an examination of the neurotransmitter systems that may play a critical role. The present proposal examines the neural processes in the prefrontal cortex important for working memory of different attributes. The first set of experiments investigates whether there are dissociations between the anterior cingulate, prelimbic/infralimbic and agranular insular in mediating working memory for spatial locations, visual objects, affect and motor responses. Based on previous studies and preliminary data, it is predicted that the anterior cingulate mediates working memory for motor responses, the prelimbic/infralimbic mediates working memory for space and objects and the agranular insular mediates working memory for affect. The second set of experiments assesses whether acetylcholine within prefrontal cortex subregions modulates working memory for different attributes. The hypothesis is that the cholinergic system is important in all prefrontal subregions for processing working memory for specific attributes. Overall, these experiments will provide a better understanding of the mnemonic functions mediated by prefrontal cortex subregions and the neurochemical modulation of these functions. Thus, the studies may increase our knowledge about the neurobiology of memory and may ultimately lead to effective treatments for cognitive dysfunctions.
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