Figure 12: Each group’s average correlations are plotted for cued, uncued and dark probes. Group differences were observed during the uncued and dark probes. The septohippocampal GABAergic system is selectively involved in spatial orientation. Direction estimation When provided access to environmental cues both groups made direct returns to the refuge. GAT1-Sap lesions disrupted homeward segment topography when access was limited to self-movement cues or environmental and self-movement cues were placed in conflict. Distance estimation When provided access to proximal environmental cues both groups modulated their peak speed relative to the distance to the refuge. GAT1-Sap lesions disrupted homeward segment kinematics when access was limited to distal environmental cues or self- movement cues. Self-movement cue processing depends on septohippocampal GABAergic function. These results add to growing literature demonstrating a selective role for limbic system structures in spatial orientation. Spatial orientation depends on a system of processes that an animal uses to navigate through space. Spatial disorientation results when there is damage to one of the neural systems that sustain these processes. For example, wandering is a behavior associated with being lost and occurs during the progression of Alzheimer’s disease (AD). AD effects the neurobiology of the central nervous system, which results in deterioration of the cholinergic projection to the hippocampus. The correlation between AD neuropathology and cognitive function has led to the development of the cholinergic hypothesis, which posits that the predominant features observed in AD may be due to a dysfunction of the cholinergic system. The cholinergic hypothesis has led researchers to develop therapies that enhance cholinergic function in those with AD. These treatments are at best, only mildly effective; therefore, an investigation of the role of other systems in AD neuropathology is needed. Identifying the function of other neurotransmitter systems will provide a more comprehensive understanding of spatial orientation, allowing for a better analysis of wandering behavior in AD and the related neuropathology. Methods Results Conclusions Role of the septohippocampal GABAergic system in spatial orientation J.R. Köppen; M. M. Sheehan; S.S. Winter; J.L. Cheatwood; D.G. Wallace Dept Psychology, Northern Illinois Univ., DeKalb, IL, USA Dept of Anatomy, Southern Illinois Univ. School of Medicine, Carbondale, IL, USA Female Long-Evans rats (n=7) were trained in a food hoarding paradigm. Initial training involved placing a “cued” refuge at the periphery of a circular table and shaping rats to carry randomly placed 1 g banana pellets back to a cued refuge. Three probes were used to dissociate environmental and self-movement cue use: 1) The uncued probe involved placing the refuge below the surface of the table, limiting rats to use distal environmental or self-movement cues to locate the refuge; 2) The dark probe involved using the hidden refuge with the room lights off, limiting rats to use self-movement cues to locate the refuge; 3) The new probe involved placing the hidden refuge on the opposite side of table, placing environmental and self-movement cues in conflict. The rats experienced the cued, hidden and dark probes twice before surgery. The rats then received either GABAergic lesions (n=2) or sham lesions (n=5). The rats were tested again in the same probes as in pre-surgery for two days. The “new” probe was given post- surgery on the last day of testing. Rats received 2 trials in the new condition. Figure 1: Photographs of the testing room are shown for dark (left) and light conditions (right). The cued refuge (17 x 26 x 12cm) is positioned at the northern edge of the table (200cm) and the uncued refuge is positioned at southern edge. Figure 3: Post-surgery homeward segment topographic profiles are plotted for representative sham (left) and GAT1-Sap (right) rats during the Cued probe. Figure 4: Each group’s average homeward segment path circuity is plotted for pre- and post- surgery testing during the Cued probe. Both groups made direct returns to refuge during post-surgery testing. Figure 7: Post-surgery homeward segment topographic profiles are plotted for representative sham (left) and GAT1-Sap (right) rats during the Dark probe. Figure 5: Post-surgery homeward segment topographic profiles are plotted for representative sham (left) and GAT1-Sap (right) rats during the Uncued probe. Figure 8: Each group’s average homeward segment path circuity is plotted for pre- and post-surgery testing during the Dark probe. The GAT1- Sap group followed circuitous paths to the refuge during post-surgery testing, relative to the Sham group. Figure 6: Each group’s average homeward segment path circuity is plotted for pre- and post- surgery testing during the Uncued probe. Both groups made direct returns to refuge during post-surgery testing. Figure 9: Post-surgery outward and homeward segment topographic profiles are plotted for representative sham and GAT1-Sap rats during the New probe. Both rats perseverate to the former refuge location (solid square) on trip 1; whereas, the GAT1-Sap rat continues to perseverate to at the former refuge location during trip 2. Trip 1 Trip 2 Correspondence: J. D. Wallace /KKK21 Introduction Sham GAT1-Saporin Figure 11: Homeward segment peak speeds are plotted relative to the homeward segment minimum distance for a representative sham and GAT1-Sap rat under cued, uncued and dark conditions. CuedUncued Dark Sham GAT1-Saporin Figure 10: Each group’s average number of progressions to the former refuge location is plotted for both trips during the New probe. Although the Sham group decreased in the number of progressions observed from Trip 1 to Trip 2, no change was observed in the GAT1-Sap group. Figure 1: Photographs of coronal sections stained for AChE or parvalbumin are presented for representative sham (left) and GAT1-Saporin (right) rats. Sham GAT1-Saporin