The role and interaction of the AT? and cholinergic systems in the nucleus basalis of meynert (NBM) effects on spatial learning /

by Wilson, Wendy L.

By Wendy L. Wilson, Ph.D. Washington State University December 2007 Chair: Jay W. Wright These experiments were designed to reveal clues regarding the relationship between the AT4 and cholinergic systems in cognitive processing. Degeneration of the cholinergic system has been hypothesized to play a significant role in Alzheimer’s disease (AD) and other dementias. The NBM is a major cholinergic area, containing a dense number of cholinergic cell bodies in addition to sending widespread projections to the neocortex. It is apparent that other neural systems are involved in the devastation of this disorder. Thus, further understanding of the neural relationships underlying normal and abnormal cognitive processing is imperative for the development of therapeutics to treat cognitive ailments. Therefore, the omnibus objectives of these studies were designed to investigate the following: 1) Is the AT4 system present in the NBM, and if so, does it play a role in cognitive processing? 2) What is the role of the iv cholinergic system in the NBM, and do these systems interact or are they autonomous systems? Findings revealed that: 1) blockade of muscarinic, nicotinic or AT4 receptors in the NBM produced significant impairments in the acquisition of the water maze task; 2) activation of the nicotinic system in the NBM reversed the AT4-antagonist induced effects; 3) activation of the muscarinic system with carbachol did not overcome AT4 antagonist-induced defecits; and 4) The AT4 agonist, Nle1-AngIV was capable of overcoming water maze acquisition deficits produced by cholinergic blockade in the NBM. Based on the collective findings of these experiments it is evident that 1) the AT4 system does play a functional role in cognitive processing via the NBM, probably a modulatory role of the cholinergic system, and 2) a complex relationship exists between the cholinergic and AT4 systems in this area. Possible explanations for the specific interaction between these two systems are discussed. v