1. Methods Results Conclusions Selective hippocampal cholinergic deafferentation disrupts exploratory trip organization D.G. Wallace*; S.K. Knapp; J.A. Silver; M.M. Martin; S.S. Winter Dept of Psychology, Northern Illinois Univ., DeKalb, IL, USA Long Evans female rats either received injections of 192 IgG- Saporin (MS SAP) or saline (SHAM) into the medial septum. Subsequent to recovery, rats were placed on a large circular table with access to a refuge under complete dark conditions (infrared cameras and goggles were used to visualize the rat). Rats were free to explore the table for 50 minutes. Exploratory sessions continued until rats made eight trips that were at least half-way across the table. Figure 1: Topographic and kinematic characteristics are plotted for a single representative exploratory trip. The searching segment of the trip is a sequence of progressions. The homeward segment is a single progression after the last stop. Figure 4: Topographic (top panels) and kinematic (bottom panels) characteristics are plotted for eight searching segments from representative SHAM (left hand panels) and MS SAP (right hand panels) rats. Figure 2: Coronal hemi-sections stained for AchE are presented for representative SHAM and SAP rats. Average cortical and hippocampal optical densities are plotted for both groups. Medial septum lesions significantly reduced markers of cholinergic function selective to the hippocampus. Figure 5: Max speed (A), path circuity (B), standard deviation of peak location (C), and stop duration (D) are plotted for each class of searching segment progressions. Groups did not differ in their searching segment characteristics. Figure 8: Max speed (A), path circuity (B), standard deviation of peak location (C), and stop duration (D) are plotted for the homeward segments. MS SAP rats’ homeward segments were significantly more circuitous, were more variable in their peak speed location, and had larger errors in distance relative to SHAM rats. Figure 6: Topographic characteristics of four trials from a representative SHAM (top panel) and MS SAP rat (bottom panel) are shown under uncued conditions. Figure 7: Topographic (top panels) and kinematic (bottom panels) characteristics are plotted for eight homeward segments from representative SHAM (left hand panel) and MS SAP (right hand panel) rats. Figure 9: Three different measures of searching segment organization were used to predict the distance error associated with the homeward segment: 1) correlation between all searching segment linear and angular speeds; 2) correlation between linear and angular speeds during periods of high angular speeds (>10 deg/sec); 3) correlation between linear and angular speeds during periods of high linear speeds (>.1m/s). Only linear-angular correlations during periods of high linear speed were predictive of homeward segment distance error. Both groups established home bases in the refuge quadrant and organized their exploration around that location. Selective hippocampal cholinergic deafferentation disrupted exploratory trip organization specific to the homeward segment. Group differences in exploratory trip organization were observed in the absence of environmental cues. These disruptions may be related to an impaired processing of self- movement cues generated on the searching segment of the exploratory trip. The novel finding that the searching segment linear-angular speed correlation (i.e., during periods of high linear speed) is predictive of distance error on the homeward segment provides further support for rats using self-movement cues to organize exploratory behavior. Correspondence: D. Wallace dwallace@niu.edu Web: www.niu.edu/user/tj0dgw1 Support Contributed By: NINDS grant NS051218 743.17 Introduction Controversy surrounds the role of hippocampal cholinergic function in spatial orientation. Non-selective medial septum lesions have been shown to disrupt performance on a variety of spatial tasks; however, the results are less conclusive when lesions are selective for cholinergic cells in the medial septum. These observations have been taken as evidence against a role of the hippocampal cholinergic function in spatial orientation. The forgoing studies typically used spatial tasks in which rats had access to environmental and self-movement cues; therefore, spared performance associated with selective lesion techniques may have reflected compensatory mechanisms rather than intact spatial orientation. The current study examines the effects of selective hippocampal cholinergic deafferentation on self- movement cue processing associated with exploratory trip organization. Figure 3: Preference for the home base quadrant (left hand panel) and total travel distance (right hand panel) are plotted for both groups. Groups were equivalent in their preference for the home base quadrant and total distance traveled. AB CD AB CD SHAMMS SAP All High Circuity No Stops R=0.140 F(1,94)=1.89, p=ns R=0.024 F(1,94)=0.055, p=ns R=0.275 F(1,94)=7.667, p<.01 R=0.219 F(1,38)=1.912, p=ns R=0.148 F(1,38)=0.847, p=ns R=0.259 F(1,38)=2.724, p=ns