Methods Results Conclusions Selective cholinergic lesions of the medial septum disrupt dead reckoning based navigation M.M. Martin*; M.D. Schultz; S.S. Winter; D.G. Wallace Dept Psychology, Northern Illinois Univ., DeKalb, IL, USA Recent investigations using selective lesion techniques have suggested that the septohippocampal cholinergic system may not be critical for spatial orientation. These studies employ spatial tasks that provide the animal with access to both allothetic and idiothetic cues; therefore, the spared performance may reflect spared spatial orientation or compensatory mechanisms associated with one class of spatial cues. The present study examined the contribution of the septohippocampal cholinergic system to spatial behavior by examining performance in foraging tasks in which cue availability was manipulated. Female Long-Evans rats either received a sham surgery (“control”) or a selective medial septum/ vertical limb of the diagonal band cholinergic lesion using the neurotoxin 192 IgG- saporin (“ms sap”). Rats were then trained to find food pellets randomly located on an open field which they then carried back to a visible refuge (“cued”) to eat. Once they became proficient at returning to their refuge, cued training was alternated with probes. The three probes included 1) replacing the visible refuge with a hidden refuge to measure ability to use cues not associated with the refuge (“uncued”); 2) testing under completely dark conditions thereby limiting access only to idiothetic cues (“dark”); and 3) moving the hidden refuge to a new location to pit use of allothetic cues against idiothetic cues (“reversal”). Trips were divided into two segments for analyses. Outward segments consisted of the moment the rat left the refuge to the moment the rat located the randomly placed food pellet. Homeward segments consisted of the moment the rat retrieved the food pellet until the rat returned to the refuge. Figure 1: Photographs of the testing room are shown with schematic overlays of the table (200 cm diameter) and refuge (17 x 26 x 12cm). Experimental conditions include: Cued (top left), Uncued (top right), Dark (bottom left), and Reversal (bottom right) shown with current refuge (gray box) and former refuge (striped box – Reversal condition only) locations. CuedUncued DarkReversal Figure 3: Topographic characteristics of four trials from a representative control (top panel) and ms sap rat (bottom panel) are shown under cued conditions. Trials were divided into outward (blue) and homeward (red) segments. Locations of the refuge (black box) and food pellets (open circles) are plotted for both rats. Figure 2: Photographs of coronal sections stained for AChE are presented from a representative control (bottom left column) and ms sap (bottom right column) rat. The reduction in AChE was restricted to the hippocampus (right figure). Figure 4: Maximum speed (left panel) and distance ratio (right panel) are plotted for outward and homeward segments under cued conditions. No group differences were observed in either measure. MS Sap Control OutwardHomeward Figure 7: Topographic characteristics of four trials from a representative control (top panel) and ms sap rat (bottom panel) are shown under dark conditions. Figure 5: Topographic characteristics of four trials from a representative control (top panel) and ms sap rat (bottom panel) are shown under uncued conditions. Figure 8: Maximum speed (left panel) and distance ratio (right panel) are plotted for outward and homeward segments under dark conditions. Both groups increased homeward maximum speeds after the first trial. Both groups also took more direct homeward paths after the first trial but overall, the control group took more direct homeward paths than the ms sap group. Figure 6: Maximum speed (left panel) and distance ratio (right panel) are plotted for outward and homeward segments under uncued conditions. No group differences were observed in either measure. OutwardHomeward MS Sap Control OutwardHomeward MS Sap Control Figure 10: Maximum speed (left panel) and distance ratio (right panel) are plotted for outward and homeward segments under reversal conditions. Both groups increased outward maximum speeds on the last trial. Both groups took more direct homeward paths after the first trial but overall, the control group reached higher homeward maximum speeds and took more direct homeward paths than the ms sap group. Figure 9: Topographic characteristics of the first two trials from a representative control (top panel) and ms sap rat (bottom panel) are shown under reversal conditions. Locations of the current refuge (black box), former refuge (striped box), and stops made by the rat after retrieving the food pellet (black triangles) are plotted for both rats. Trip 1 Trip 2 MS Sap Control No group differences were observed when rats were provided access to both allothetic and idiothetic cues under cued and uncued conditions. The MS Sap group was impaired when visual allothetic cues were unavailable under dark conditions. When allothetic and idiothetic cues were put in conflict, the MS Sap group was impaired in returning to the new refuge location under reversal conditions. Results are consistent with MS Sap lesions producing a selective impairment in idiothetic cue processing, and suggests that these rats were able to use allothetic cues to compensate under cued and uncued conditions. Correspondence: M. Martin D. Wallace Web: Support Contributed By: NINDS grant NS Abstract