Maternal immune activation alters nonspatial information processing in the hippocampus of the adult offspring.
The observation that maternal infection increases the risk for schizophrenia in the offspring suggests that the maternal immune system plays a key role in the etiology of schizophrenia. In a mouse model, maternal immune activation (MIA) by injection of poly(I:C) yields adult offspring that display abnormalities in a variety of behaviors relevant to schizophrenia. As abnormalities in the hippocampus are a consistent observation in schizophrenia patients, we examined synaptic properties in hippocampal slices prepared from the offspring of poly(I:C)- and saline-treated mothers. Compared to controls, CA1 pyramidal neurons from adult offspring of MIA mothers display reduced frequency and increased amplitude of miniature excitatory postsynaptic currents. In addition, the specific component of the temporoammonic pathway that mediates object-related information displays increased sensitivity to dopamine. To assess hippocampal network function in vivo, we used expression of the immediate-early gene, c-Fos, as a surrogate measure of neuronal activity. Compared to controls, the offspring of poly(I:C)-treated mothers display a distinct c-Fos expression pattern in area CA1 following novel object, but not novel location, exposure. Thus, the offspring of MIA mothers may have an abnormality in modality-specific information processing. Indeed, the MIA offspring display enhanced discrimination in a novel object recognition, but not in an object location, task. Thus, analysis of object and spatial information processing at both synaptic and behavioral levels reveals a largely selective abnormality in object information processing in this mouse model. Our results suggest that altered processing of object-related information may be part of the pathogenesis of schizophrenia-like cognitive behaviors.
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Hiroshi T
HT
Ito
Stephen E P
SE
Smith
Elaine
E
Hsiao
Paul H
PH
Patterson
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000502:physiology; D003071:Cognition / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D004594:Electrophysiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D006624:Hippocampus / Q000276:immunology* / Q000502:physiology*; D007109:Immunity / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000473:pathology; D011070:Poly I-C / Q000494:pharmacology; D011247:Pregnancy; D017966:Pyramidal Cells / Q000502:physiology; D021641:Recognition, Psychology / Q000502:physiology; D012559:Schizophrenia / Q000139:chemically induced; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D011070:Poly I-C; D004298:Dopamine