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.
Highlights
Stranded RNA, or with the TLR4 agonist, Gram-negative lipopolysaccharide (LPS), produces brain and behavior changes that feature some aspects of neurodevelopmental disorders such as schizophrenia and autism[19]
Intrinsic excitability properties of hippocampal neurons cultured from neonatal offspring of polyI:C- and saline-treated pregnant rats
The main findings of this study indicate that in the poly I:C model of maternal immune activation (MIA), extremely early functional abnormalities occur in hippocampal neurons cultured from neonatal offspring of poly I:C-treated moms compared to those derived from offspring of saline-treated mothers
Summary
Stranded RNA, or with the TLR4 agonist, Gram-negative lipopolysaccharide (LPS), produces brain and behavior changes that feature some aspects of neurodevelopmental disorders such as schizophrenia and autism[19]. Extracellular and intracellular recording data indicated that MIA leads in the offspring to hippocampal alterations in synaptic transmission and long-term plasticity[40,41,42,43,44,45,46] These studies yielded inconsistent results and no work examined the impact of MIA on the intrinsic excitability of hippocampal pyramidal neurons. These previous investigations were performed only in juvenile or adult animals. It is unknown whether neurophysiological alterations following MIA could occur earlier in neonatal/ early postnatal hippocampal neurons. Our data suggest that maternal immune activation leads to neurophysiological abnormalities in hippocampal neurons derived from neonatal offspring animals
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