Selective lesion of septal cholinergic neurons in rats impairs acquisition of a delayed matching to position T-maze task by delaying the shift from a response to a place strategy

Abstract

This study tested the hypothesis that septal cholinergic lesions impair acquisition of a delayed matching to position (DMP) T-maze task in male rats by affecting learning strategy. Rats received either the selective cholinergic immunotoxin, 192 IgG-saporin (SAP) or artificial cerebrospinal fluid directly into the medial septum. Two weeks later, animals were trained to acquire the DMP task. SAP-treated rats took significantly longer to acquire the task than corresponding controls. Both SAP-treated and control rats adopted a persistent turn and utilized a response strategy during early periods of training. By the time rats reached criterion the persistent turn was no longer evident, and all rats had shifted to an allocentric strategy, i.e., were relying on extramaze cues to a significant degree. During the acquisition period, SAP-treated rats spent significantly more days showing a persistent turn and using a response strategy than corresponding controls. The added time spent using a response strategy accounted entirely for the added days required to reach criterion among the SAP-treated rats. This suggests that the principal mechanism by which septal cholinergic lesions impair DMP acquisition in male rats is by increasing the predisposition to use a response vs. a place strategy, thereby affecting the ability to switch from one strategy to another.

Figure 1

Acquisition of the DMP task. Training was blocked into 5 day periods with each point representing t. The performance of both treatment groups (Control n = 9 and SAP n = 8) improved over time. During periods 3 and 4 (days 11–15 and 16–20 respectively) the performance of control was significantly better than the SAP group ** p < 0.01).

Figure 2

Comparison of the mean ± S.E.M., numbers of days to reach criterion for control and SAP treated rats. SAP-treated rats took significantly longer to reach criterion on the DMP task than corresponding controls (21.6 ± 1.3 days vs. 16.0 ± 0.4 days; ** p < 0.01)

Figure 3

Comparison of the mean ± S.E.M., total number of days that rats adopted a persistent turn was significantly greater for SAP treated rats than for controls (14.78 ± 1.76 days vs. 8.13 ± 1.66 days ** p < 0.01)

Figure 4

Figures: 4A and 4B. Disruption of persistent turning strategy (failure to turn in the same direction at least 7 of 8 trials during the open choice trials). There was no significant effect of rotating the T-maze 180° in either control or SAP treatment groups (p > 0.05; Fisher’s Exact test) indicating that spatial cues were not a significant factor for either control or SAP treated animals when using a response strategy to navigate the T-maze. 4C and 4D. Disruption of place strategy (failure to return to goal arm during open choice trial for at least 7 of 8 trial pairs). There was a disruption in navigation by rotating the T-maze 180°, in both control and SAP treated groups (p < 0.002; Fisher’s Exact test) This result indicates that visual spatial cues played a significant role in navigation for both treatment groups once the rats achieved criterion in the DMP T-maze task.