ELEVATED MATERNAL IMMUNE SIGNALING ALTERS CELL-SPECIFIC TRANSCRIPTOMIC PROFILES IN VMPFC–AMYGDALA CIRCUITRY IN NONHUMAN PRIMATE OFFSPRING

Prenatal exposure to an activated maternal immune system can affect offspring brain and behavioral development and increase the risk of neurodevelopmental disorders, yet the long-term cellular and molecular changes in the brain remain poorly understood. To address this gap, we induced maternal immune activation (MIA) with the viral mimic Poly:IC/LC in rhesus macaques, a species with critical anatomical and developmental similarities to humans, and collected imaging, immune, and behavioral data from 27 offspring from birth to 4 years of age (14 control, 13 MIA). MIA offspring displayed aberrant social behavior that, along with preliminary cellular findings, suggests atypical development of the amygdala and prefrontal cortices (PFC). We performed single-nucleus RNA sequencing at 4 years of age in ventromedial PFC and amygdala subnuclei (lateral, central, accessory basal) to identify impacted cell types and cell-specific gene expression changes. Precise anatomical sampling was guided by adjacent immuno-labeled sections. Following combinatorial barcoding and sequencing, we identified distinct cell-type clusters and assessed cell-type specific differential gene expression (DGE) and pathway enrichment. Excitatory neuron clusters, particularly DPP10- and HTR2A-enriched populations in lateral and accessory basal amygdala, showed the greatest numbers of DEGs, with fewer but notable DEGs in inhibitory neurons and glial subtypes across regions. In vmPFC, excitatory neurons, especially L2/3–6 IT clusters, were most affected. Across regions, DEGs converged on pathways related to axon guidance, synaptic architecture, and ion regulation, revealing long-term molecular alterations within vmPFC–amygdala circuitry years after gestational exposure to an altered maternal immune environment.