Acquisition Of Spatial Navigation Research Articles

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 destroy granule cells. This study compared the behavioral effects of various amounts of colchicine (1.0, 3.0, and 6.0 μg; Col 1, Col 3, and Col 6, respectively) injected into the dentate gyrus of adult Long-Evans male rats. Starting 10 days after lesion surgery, behavioral testing assessed home-cage and open-field locomotion, alternation in a T-maze, water-maze, and radial-maze learning according to protocols placing emphasis on reference, and working memory. All of these tasks are sensitive to hippocampal disruption. Histological verifications showed that the extent of the lesions depends on the dose of colchicine (index of dentate gyrus shrinkage: −33% in Col 1, −54% in Col 3, and −67% in Col 6 rats). Colchicine dose-dependently increased nocturnal home cage activity (an effect found 10 days but not 5 months after surgery), but had no significant effect on open-field locomotion or T-maze alternation. A dose-dependent reference memory impairment was found during the acquisition of spatial navigation in the water maze; Col 3 and Col 6 rats were more impaired than Col 1 rats. During the probe trial (platform removed), 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 deficits were larger in Col 3 and Col 6 rats compared to Col 1 rats. The lesions had no effect on swimming speed. In the radial-maze test, there was also a dose-dependent working memory impairment. However, reference memory was disrupted in a manner that did not differ among the three groups of lesioned rats. Our data are in line with the view that the dentate gyrus plays an important role in the acquisition of new information and is an integral neural 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 demonstrate that part of the variability in the conclusions from previous experiments concerning the role of granule cells in cognitive processes, particularly in spatial learning and memory, may be due to the type of tests used and/or the extent of the damage produced.

Tetrahydroaminoacridine, a cholinesterase inhibitor, and D-cycloserine, a partial NMDA receptor-associated glycine site agonist, enhances acquisition of spatial navigation.

The present study examines the efficacy of single and combined treatments with an antiocholinesterase, tetrahydroaminoacridine (THA, i.p.), and a glycine-B site partial agonist, D-cycloserine (DCS, i.p.) to alleviate water maze (WM) spatial navigation defect induced by medial septal (MS) lesion. THA 3 and DCS at 3 or 10 mg/kg improved acquisition of the WM test, but only DCS improved spatial bias. These drugs had no effect on consolidation. A combination of THA 3 and DCS 10 mg/kg enhanced WM acquisition more effectively than either of the treatments on their own. This suggests that combined modulation of acetylcholine and NMDA mechanisms may have greater therapeutic effect to stimulate cognitive dysfunctions.

Early postnatal alcohol exposure that produces high blood alcohol levels impairs development of spatial navigation learning

Artificial rearing procedures were used to expose groups of rats to alcohol during Postnatal Days 4 to 10. A 6.6-g/kg daily dose of ethanol was given either in a condensed fashion to induce cyclic daily blood alcohol concentrations (BACs) with high peaks or in a uniform fashion to induce stable, moderate daily BACs. Control groups included a gastrostomized, artificially reared group not exposed to alcohol and a suckle group. All artificially reared pups were fostered back to a dam on Postnatal Day 12. Beginning on Postnatal Day 19, the rats were tested daily in the Morris maze spatial navigation task. All measures of spatial navigation performance indicated that the group given the condensed alcohol exposure was significantly impaired in acquisition of spatial navigation. The group given uniform alcohol exposure differed only mildly from the control groups. The impairment of place learning of the condensed alcohol group suggests that the development of the hippocampal formation may have been impaired, consistent with findings that the neuromorphology of the hippocampus is significantly affected by condensed early postnatal alcohol exposure.