Individuals with schizophrenia display a number of structural and cytoarchitectural alterations in the hippocampus, suggesting that functional processes such as synaptic plasticity may also be modified. Altered hippocampal plasticity is likely to affect memory function, and may therefore contribute to the cognitive symptoms of schizophrenia.
Our goal was to determine whether environmental risk factors that have previously been associated with schizophrenia produced changes in hippocampal synaptic plasticity and associated memory processes, using the maternal immune activation (MIA) animal model. Pregnant rat dams were administered either Poly I:C or vehicle on GD15 to initiate MIA. Long-term potentiation (LTP) was measured in the dentate gyrus of their freely-moving, adult offspring.
The memory performance of these animals was also tested in the Morris water-maze and in a plus-maze. MIA did not alter basal synaptic transmission in either the dentate gyrus or CA1 of freely moving adult rats. It did, however, result in increased paired-pulse facilitation of the dentate gyrus population spike and an enhanced persistence of dentate LTP across several days. MIA animals also displayed slower reversal learning in both the water maze, and the plus maze.
MIA animals displayed a reduced flexibility to change behavior in response to changes in task requirements. The effect could result from more persistent memory for the original goals, an interpretation that corresponds well with the LTP data. The results support the hypothesis that hippocampal plasticity is altered in schizophrenia and that this may underlie aspects of cognitive dysfunction in this disorder. Supported by funding from the Health Research Council of New Zealand.
