For many years, most research relating to the severe memory disturbances associated with AD has been based on those neurochemical or neuropathological changes that occur specifically within the cholinergic nervous system. Unfortunately, attempts to limit or ameliorate the memory dysfunction in AD using treatments that address only the cholinergic nervous system have not been as effective as anticipated. It is becoming increasingly clear that other neurotransmitter systems, including the serotonergic and noradrenergic systems, are affected in AD. In addition, these same neurotransmitter systems have been implicated in the control of learning and memory. Moreover, biochemical and functional interactions appear to exist between neurotransmitter systems. Accordingly, it is very possible that multiple neurotransmitter dysfunctions may be may be responsible for the behavioral manifestations of the disease. Unfortunately, little information exists as to how, and what degree, neurotransmitter systems interact in the control of information processing. Likewise, little information exists as the functional significance of impairments in activity of multiple neurotransmitter systems. Considerable multidisciplinary work is required to identify and characterize the interactions that exist between neurotransmitter systems in the control of information processing in order to determine how a dysfunction is this interaction contributes to geriatric-related memory disorders, and before rational treatment strategies based on multiple neurotransmitter systems can be designed to prevent, limit or correct the memory disturbances in AD. The goal of the purposed research is to (1) systematically examine the functional interactions that may exist between the cholinergic, serotonergic and noradrenergic neurotransmitter systems in normal information processing, and (2) determine whether a disruption in the function of multiple neurotransmitter systems should be considered in the etiology, symptomatology and treatment of AD. These goals will be accomplished by experiments designed to characterize the functional interactions that exist between the cholinergic, serotonergic and noradrenergic nervous systems in a) normal information processing, b) the memory deficits normally exhibited by aged animals, and c) the memory deficits observed in the current cholinergic animal model that mimics certain aspects of AD.
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