Cognitive performances and locomotor activity following dentate granule cell damage in rats: Role of lesion extent and type of memory tested

Intradentate injection of colchicine is one of the techniques used to destr oy granule cells. This study compared the behavioral effects of various amo unts of colchicine (1.0, 3.0, and 6.0 mug; Col 1, Col 3, and Col 6, respect ively) injected into the dentate gyrus of adult Long-Evans male rats. Start ing 10 days after lesion surgery, behavioral testing assessed home-cage and open-field locomotion, alternation in a T-maze, water-maze, and radial-maz e learning according to protocols placing emphasis on reference, and workin g memory. All of these tasks are sensitive to hippocampal disruption. Histo logical verifications showed that the extent of the lesions depends on the dose of colchicine (inder of dentate gyrus shrinkage: -33% in Col 1, -54% i n Col 3, and -67% in Col 6 rats). Colchicine dose-dependently increased noc turnal home cage activity (an effect found 10 days but not 5 months after s urgery), but had no significant effect on open-field locomotion or T-maze a lternation. A dose-dependent reference memory impairment was found during t he acquisition of spatial navigation in the water maze; Col 3 and Col 6 rat s were more impaired than Col 1 rats. During the probe trial (platform remo ved), control rats spent a longer distance swimming over the platform area than all rats with colchicine lesions. In the working memory version of the test, all rats with colchicine lesions showed significant deficits. The de ficits were larger in Col 3 and Col 6 rats compared to Col 1 rats. The lesi ons had no effect on swimming speed. In the radial-maze test, there was als o a dose-dependent wet-king memory impairment. However, reference memory wa s disrupted in a manner that did not differ among the three groups of lesio ned rats. Our data are in line with the view that the dentate gyrus plays a n important role in the acquisition of new information and is an integral n eural substrate for spatial reference and spatial working memory. They also suggest that damage to granule cells might have more pronounced effects on reference than on working memory in the radial maze. Finally, they demonst rate that part of the variability in the conclusions from previous experime nts concerning the role of granule cells in cognitive processes, particular ly in spatial learning and memory, may be due to the type of tests used and /or the extent of the damage produced. (C) 2001 Academic Press.