title: Enhanced hippocampal neuronal excitability and LTP persistence associated with reduced behavioral flexibility in the maternal immune activation model of schizophrenia.
abstract: Individuals with schizophrenia display a number of structural and cytoarchitectural alterations in the hippocampus, suggesting that other functions such as synaptic plasticity may also be modified. Altered hippocampal plasticity is likely to affect memory processing, and therefore any such pathology may contribute to the cognitive symptoms of schizophrenia, which includes prominent memory impairment. The current study tested whether prenatal exposure to infection, an environmental risk factor that has previously been associated with schizophrenia produced changes in hippocampal synaptic transmission or plasticity, using the maternal immune activation (MIA) animal model. We also assessed performance in hippocampus-dependent memory tasks to determine whether altered plasticity is associated with memory dysfunction. 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 long-term potentiation. MIA animals displayed slower learning of a reversed platform location in the water maze, and a similarly slowed learning during reversal in a spatial plus maze task. Together these findings are indicative of reduced behavioral flexibility in response to changes in task requirements. The results are consistent with the hypothesis that hippocampal plasticity is altered in schizophrenia, and that this change in plasticity mechanisms may underlie some aspects of cognitive dysfunction in this disorder.
authors: Department of Psychology and the Brain Health Research Center, University of Otago, Dunedin, New Zealand.
authors: Shakuntala
authors: S
authors: Savanthrapadian
authors: Amy R
authors: AR
authors: Wolff
authors: Barbara J
authors: BJ
authors: Logan
authors: Michael J
authors: MJ
authors: Eckert
authors: David K
authors: DK
authors: Bilkey
authors: Wickliffe C
authors: WC
authors: Abraham
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D018782:Maze Learning / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011119:Polynucleotides / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000209:etiology / Q000473:pathology*; D013028:Space Perception / Q000187:drug effects / Q000502:physiology
chemical_list: D011119:Polynucleotides; C049667:poly(rI).poly(dC)
keywords: cognitive flexibility; dentate gyrus; spatial memory; synaptic inhibition; synaptic plasticity