Maternal immune activation impairs hippocampal pyramidal neuron excitability in newborn rat offspring: Implications for neurodevelopmental disorders

Maternal infection during pregnancy is associated with an increased risk of neurodevelopmental disorders, including depression, schizophrenia, and autism spectrum disorder. The hippocampus plays a critical role in these disorders, but the impact of maternal immune activation (MIA) on early hippocampal neuron function remains poorly understood. We investigated the effects of lipopolysaccharide-induced MIA in pregnant rats (20–80 μg/kg on gestational days 15–19) on the electrophysiological properties of hippocampal pyramidal neurons from newborn offspring. Primary neuronal cultures were prepared from the hippocampi of newborn rats and maintained for 13 days in vitro (DIV13). Whole-cell patch-clamp recordings assessed neuronal excitability parameters between DIV4-13. MIA significantly altered action potential characteristics in offspring hippocampal neurons, including: (1) increased latency time, threshold potential, and repolarization potential; (2) decreased peak potential, ascend and descend velocities; and (3) reduced spontaneous and evoked firing frequencies. These alterations suggest impaired glutamatergic neurotransmission in the hippocampus of MIA offspring, with potential sex-specific effects observed for spontaneous activity. Our findings demonstrate that MIA significantly decreases the excitability of hippocampal pyramidal neurons in newborn offspring. This reduced glutamatergic neurotransmission may contribute to the pathophysiology of neurodevelopmental disorders associated with maternal infection during pregnancy. This study provides novel insights into early neurophysiological changes following prenatal immune challenge that may inform therapeutic interventions targeting hippocampal function.