| The septohippocampal cholinergic (SHC) system appears to be a critical neural substrate for memory processes. This system directly modulates the neurophysiological activity of the hippocampus (HPC), and in doing so influences the cognitive processes subserved by activity within that structure. Ethylcholine aziridinium ion (AF64A) is a neurotoxic analog of choline that can selectively alter cholinergic function in vivo. Its use has been proposed as a neurochemical tool for examining the neurobiological function of central cholinergic systems and for developing an animal model of central cholinergic hypofunction with relevance to human dementias with an underlying cholinergic pathology, i.e., Alzheimer's Disease. The present set of studies examined the mnemonic impairments resulting from intraventricular administration of AF64A. In addition, these studies examined the neurochemical and histological consequences of this treatment, as well as the viability of cholinomimetic strategies for attenuating the associated mnemonic impairments. The results of these studies demonstrated that a select impairment in working/episodic memory processes occurs following an AF64A-induced alteration of SHC activity, and that this mnemonic impairment is specifically related to the compounds cholinotoxic properties. Further, several cholinomimetic strategies failed to attenuate the AF64-induced mnemonic impairments. The neurobiological function of the septohippocampal system, the usefulness of AF64A as a tool for inducing a central cholinergic hypofunction, and the relevance of cholinomimetic replacement strategies for attenuating impairments associated with cholinergic hypofunction are discussed. |
