Click to Enlarge

The hippocampus has been extensively studied by neuropsychological, anatomical and physiological methods. In recent work (Neuron 22:233-242, 1999), I have attempted to bring this work into a coherent model. I argued that the dentate gyrus forms a new representation of incoming information and that the dentate and CA3 then work together on this information to store memory sequences in context. Crucial to this idea is that learned sequences are useful in making predictions about the future. During recall, these predictions are sent to CA1, where they can be compared to current sensory information that arrives at CA1 directly from cortex (the distal perforant path input to CA1). We want to understand this comparator function. Towards this end, we have been studying how the perforant path input is gated by neuromodulators. Our work shows that dopamine can selectively block the perforant path input to CA1, while having little effect on the direct input from CA3. The next step is to understand the dendritic processes involved in the interaction of these two inputs. The understanding of the comparator function of CA1 is likely to have important implications for schizophrenia, since some of the symptoms of schizophrenia can be traced to processing abnormalities in the hippocampus.