Maternal Immune Activation in Pregnant Mice Produces Offspring with Altered Hippocampal Ripples

Abstract

Psychiatric disorders, such as schizophrenia and autism spectrum disorder, are associated with sleep disturbances and deficits in memory consolidation; however, the relationship between these symptoms remains unclear. Here, we focused on hippocampal sharp-wave ripples (SWRs), a form of transient high-frequency oscillations that occur during sleep and behavioral immobility and contribute to memory consolidation. We activated the maternal immune system with polyinosinic–polycytidylic acid (poly(I : C)), one of the major pharmacological models of psychiatric disorders, to investigate whether SWR activity is altered in acute slices of the hippocampus from offspring born to poly(I : C)-treated mouse dams. Using robust continuous clustering in a low dimensional space defined by a uniform manifold approximation and projection, we found that mice with prenatal exposure to poly(I : C) exhibited different feature distributions of SWR waveforms without affecting the overall frequencies of SWR events. Based on our results, maternal immune activation leads to altered SWR patterns in offspring.

Graphical Abstract