Learning deficits after lesions of dentate gyrus granule cells.

The effect of destroying granule cells in the dentate gyrus on learning was examined with a behavioral testing protocol. These neurons were destroyed by microinjections of the selective neurotoxin colchicine in the hippocampal formation of rats. After a 30-day recovery period, the animals were trained in an operant chamber with an appetitive conditioning paradigm. The learning abilities of the animals with lesions were compared with two control groups--naive, unoperated rats and those with control injections of saline. The basic task required the animal to discriminate between two spatially separate visual stimuli which represented positive and negative cues. Testing and training was separated into four progressively more difficult phases with various stimulus schedules, contingencies of reinforcement, and stimulus positions. Colchicine-treated animals demonstrated significantly poorer performance than naive animals and those receiving saline control injections. None of the colchicine-treated animals achieved criterion performance in the stimulus position reversal paradigm, and half had difficulty with variable ratio schedules of reinforcement. Our experiments suggested that granule cells in the dentate gyrus played a pivotal role in certain learning tasks.