Grant: Master's Award: Canada Graduate Scholarships

Behavioural Neuroscience; Maternal Immune Activation; Microglia; Mouse; Neurodevelopmental Disorders; Polyriboiosinic-Polyribocyidilic Acid; Vagus Nerve Stimulation

Vagus nerve stimulation (VNS) is a therapeutic modality for some psychiatric disorders, but its effects on neurodevelopmental disorders (NDDs), like schizophrenia, are largely unknown. Microglia, the brains immune cells, play key roles in normal development. Early life adversities, such as maternal immune activation (MIA), can trigger abnormal microglial responses, contributing to the emergence of NDDs. VNS can reduce microglial abnormal inflammatory responses, rescuing the MIA effects during brain development. However, the mechanisms by which VNS exerts its beneficial outcomes on NDDs have remained elusive. We hypothesize that VNS will normalize MIA-compromised microglial developmental roles and prevent neurodevelopment abnormalities. Using a mouse model, dams will undergo VNS throughout gestation as a preventive strategy and will be injected with a viral-mimetic substance in early gestation, at the embryonic day 9.5, to induce schizophrenia-like phenotypes in the offspring. Behavioural testing for sociability, cognition, and sensorimotor processing—often impacted by NDDs—will be performed in developmental ages corresponding to infancy, adolescence, and adulthood. Confocal microscopy will examine microglial density, distribution, morphology and colocalization with functional states-related markers, such as phagocytic and dystrophic markers. 3D-scanning electron microscopy will examine microglial interactions with synapses at the ultrastructural level. Our analysis will focus on the prefrontal cortex and hippocampus due to their involvement in the MIA-induced NDD's behavioural and neuroimmune abnormalities. This project will provide transformative insights into the impact of VNS as a novel approach to prevent microglial alterations triggered by MIA during development.