Johaly Anguiano-Buenfil, Isabel Sollozo-Dupont, Luis A Márquez, Angelica Zepeda, Emilio J Galván
Viral infections during critical periods of pregnancy trigger inflammatory responses that alter offspring brain development and behavior, resulting in psychiatric disorder-associated phenotypes. This condition is commonly referred to as prenatal stress induced by maternal immune activation (MIA). Here, we investigate the effects of MIA on the neurophysiological properties of the dentate gyrus-CA3 circuit, a hippocampal circuit critical for cortical input processing and memory formation, and increasingly implicated in psychiatric disorders. Pregnant Sprague-Dawley dams were systemically administered polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA that elicits a viral-like immune response by activating the Toll-like receptor 3 (TLR3)-NF-kB signaling pathway. Extracellular recordings were performed on acute slices of male offspring at postnatal days 61-80. MIA increased the antidromic population spike amplification at the mossy fiber (MF)-granule cell layer response without modifying the antidromic responses at the CA3-CA3 commissural-associational fibers. Paired pulses with short interstimulus intervals revealed decreased levels of phasic and tonic GABAergic inhibition. In addition, MIA reduced coupling between presynaptic fiber volleys and MF field excitatory postsynaptic potentials (MF fEPSP). At the level of synaptic plasticity, MIA impaired frequency-dependent facilitation and decreased MF fEPSP paired-pulse facilitation, two hallmark forms of short-term plasticity at the MF-CA3 synapse. Lastly, MF-mediated long-term potentiation (MF LTP) and long-term depression (MF LTD) showed altered magnitudes in MIA slices. Collectively, our results indicate that MIA alters neuronal processing and output in the DG-CA3 hippocampal network, supporting the contribution of maternal inflammation to long-term circuit dysfunction associated with viral infections during pregnancy.