A proposed pathological model in the hippocampus of subjects with schizophrenia

1. The hippocampal formation plays an important role in the normal function ing of the brain, being implicated in cognition and sensory gating, both of which are affected in schizophrenia. The hippocampal formation receives in formation from the association cortices, which is processed by glutamatergi c transmission within the hippocampus, Dopamine, noradrenaline, 5-hydroxytr yptamine (5-HT), acetylcholine and GABA, all of which have been proposed to play a role in the neurobiology of schizophrenia, can affect this transmis sion. 2. The advent of the 'atypical' antipsychotics, with their broad pharmacolo gical spectra and improved therapeutic outcome, has revitalized research in to neurotransmitter dysfunction other than that of dopamine. In particular, there has been interest in the serotonergic and cholinergic systems within the hippocampal formation because these are two of the transmitter systems targeted by clozapine and olanzapine, 3. From the study of these systems, using tissue obtained post-mortem from subjects with schizophrenia, we propose that there is a hyperserotonergic s tate in the hippocampal formation of some subjects with schizophrenia cause d by a conformational change in the 5-HT transporter, The model we propose allows us to construct further studies that will test the consequences of s uch a hyperserotonergic state in the hippocampal formation. This model has the potential to open new avenues in schizophrenia research.