title: Maternal immune activation produces neonatal excitability defects in offspring hippocampal neurons from pregnant rats treated with poly I:C.
abstract: Maternal immune activation (MIA) resulting from prenatal exposure to infectious pathogens or inflammatory stimuli is increasingly recognized to play an important etiological role in neuropsychiatric disorders with neurodevelopmental features. MIA in pregnant rodents induced by injection of the synthetic double-stranded RNA, Poly I:C, a mimic of viral infection, leads to a wide spectrum of behavioral abnormalities as well as structural and functional defects in the brain. Previous MIA studies using poly I:C prenatal treatment suggested that neurophysiological alterations occur in the hippocampus. However, these investigations used only juvenile or adult animals. We postulated that MIA-induced alterations could occur earlier at neonatal/early postnatal stages. Here we examined the neurophysiological properties of cultured pyramidal-like hippocampal neurons prepared from neonatal (P0-P2) offspring of pregnant rats injected with poly I:C. Offspring neurons from poly I:C-treated mothers exhibited significantly lower intrinsic excitability and stronger spike frequency adaptation, compared to saline. A similar lower intrinsic excitability was observed in CA1 pyramidal neurons from hippocampal slices of two weeks-old poly I:C offspring. Cultured hippocampal neurons also displayed lower frequency of spontaneous firing, higher charge transfer of IPSCs and larger amplitude of miniature IPSCs. Thus, maternal immune activation leads to strikingly early neurophysiological abnormalities in hippocampal neurons.
authors.affiliation: Department of Physiology &Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.|Department of Psychology, Gordon Faculty of Social Sciences, Tel Aviv University, Tel Aviv 69978, Israel.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Eti
authors.initials: E
authors.lastname: Patrich
authors.affiliation: Strauss Center for computational Neuroimaging, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Piontkewitz
authors.affiliation: Department of Physiology &Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Asher
authors.initials: A
authors.lastname: Peretz
authors.affiliation: Department of Psychology, Gordon Faculty of Social Sciences, Tel Aviv University, Tel Aviv 69978, Israel.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ina
authors.initials: I
authors.lastname: Weiner
authors.affiliation: Department of Physiology &Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.|Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Bernard
authors.initials: B
authors.lastname: Attali
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D000956:Antigens, Viral / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D007113:Immunity, Innate / Q000187:drug effects*; D011070:Poly I-C / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology / Q000473:pathology; D061251:Primary Cell Culture; D017966:Pyramidal Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051381:Rats
chemical_list: D000956:Antigens, Viral; D011070:Poly I-C