Infusion of GAT1-saporin into the medial septum/vertical limb of the diagonal band disrupts self-movement cue processing and spares mnemonic function

Abstract

Degeneration of the septohippocampal system is associated with the progression of Dementia of the Alzheimer's type (DAT). Impairments in mnemonic function and spatial orientation become more severe as DAT progresses. Although evidence supports a role for cholinergic function in these impairments, relatively few studies have examined the contribution of the septohippocampal GABAergic component to mnemonic function or spatial orientation. The current study uses the rat food-hoarding paradigm and water maze tasks to characterize the mnemonic and spatial impairments associated with infusing GAT1-Saporin into the medial septum/vertical limb of the diagonal band (MS/VDB). Although infusion of GAT1-Saporin significantly reduced parvalbumin-positive cells in the MS/VDB, no reductions in markers of cholinergic function were observed in the hippocampus. In general, performance was spared during spatial tasks that provided access to environmental cues. In contrast, GAT1-Saporin rats did not accurately carry the food pellet to the refuge during the dark probe. These observations are consistent with infusion of GAT1-Saporin into the MS/VDB resulting in spared mnemonic function and use of environmental cues; however, self-movement cue processing was compromised. This interpretation is consistent with a growing literature demonstrating a role for the septohippocampal system in self-movement cue processing.