Neurochemical Modulation of the Hippocampus in Learning, Remembering and Forgetting in Primates

Information about the outside world is carried into the hippocampus by glutamatergic pyramidal cell pathways from the posterior association cortex via the subiculum. Processed information is carried away from the hippocampus by a reciprocal glutamatergic pathway back into posterior association cortex. These pathways are thought to be crucial for the acquisition of long term memories although it seems likely that memories are stored in cortex rather than within the hippocampus. The hippocampus is supported by functionally excitatory cholinergic modulation via fornical afferents and by functionally inhibitory serotonergic modulation specifically via 5HT_1Areceptors. Cholinergic modulation of the hippocampus is necessary for efficient acquisition of visuospatial tasks but not for retention of similar tasks first acquired prior to surgery. Cholinergic modulation of areas outside the hippocampus may contribute to the maintenance of memories and non-cholinergic efferents in the fornix may be required for retrieval of tasks first learnt when the hippocampus was intact. Impairments on acquisition of visuospatial tasks brought about by fornix transection can be ameliorated by direct stimulation of cholinergic receptors using pilocarpine or by blockade of the serotonergic inhibitory modulation of the hippocampus using the 5HT_1Areceptor antagonist, WAY100635, indicating an equal-but-opposite modulatory effect of these two neurotransmitters on hippocampal function.