Hippocampal encoding of non-spatial trace conditioning.

Trace eyeblink classical conditioning is a non-spatial learning paradigm that requires an intact hippocampus. This task is hippocampus-dependent because the auditory tone conditioned stimulus (CS) is temporally separated from the corneal airpuff unconditioned stimulus (US) by a 500-ms trace interval. Our laboratory has performed a series of neurophysiological experiments that have examined the activity of pyramidal cells in the CA1 area of the hippocampus during trace eyeblink conditioning. We have found that the non-spatial stimuli involved in this paradigm are encoded in the hippocampus in a logical order that is necessary for their association and the subsequent expression of behavioral learning. Although there were many profiles of single neurons responding to the CS-US trial during training, the majority of the neurons showed an increase in activity to the airpuff-US. Prior to learning, it appears that hippocampal cells and ensembles of cells were preferentially attending to the stimulus with immediate behavioral importance, the US. Hippocampal cells then began to respond to the associated neutral stimulus, the CS. Shortly thereafter, animals began to show increases in the behavioral expression of CRs. In some experiments, hippocampal neurons from aged animals exhibited impairments in the encoding of CS and US information. These aged animals were not able to associate these stimuli and acquire trace eyeblink CRs. Our findings along with the findings of other spatial learning studies, suggest that the hippocampus is involved in encoding information about discontiguous sets of stimuli, either spatial or nonspatial, especially early in the learning process.