PROJECT SUMMARY/ABSTRACTIntimate partner violence (IPV) increases the risk of traumatic brain injury (TBI) because the physical assaultstarget the head neck and face. Women more than men across socioeconomic racial educational regionaland other demographic variables are in harms way throughout their life and particularly during pregnancy. Whenone partner is pregnant the frequency and intensity of physical assaults increase and remain focused on thehead neck and face. But the consequences of a TBI during pregnancy (gravida TBI; gTBI) on offspring neuro-development are unknown. Isolated TBI elevates stress and inflammation which are known to divert fetal neuro-development with gestational exposure. The proposal goal is to provide proof-of-concept that gTBI can disturbneurodevelopment thereby establishing gTBI as an environmental risk factor for developmental disorders.These studies cannot be performed in people or be derived from existing databases thereby warrantinglaboratory studies. Preliminary data from this research team showed live births low male weaning weightdistorted cortical circuity reduced anxiety and depression and a muted immune response principally in malegTBI offspring. These results encourage further investigation of TBI timing with respect to pregnancy broaderassessment of neuropsychiatric outcomes enhanced neural circuit analyses and molecular investigations ofcell and synaptic change. The extent of neurodevelopment disruption is compared to a standard model ofmaternal immune activation (MIA) and respective controls. The central hypothesis of this proposal is that TBIduring pregnancy leads to disrupted neurodevelopmental trajectory in the offspring that includes alteredneurobehavioral performance neurocircuit organization and cell type-specific molecular disturbances.To test this hypothesis a diffuse TBI will be delivered to timed-pregnant mice at 5 and 12 days post-coitum andthen follow male and female offspring in terms of: [Aim 1] birth outcomes offspring physiology neurobehavioralphenotype; [Aim 2] neurocircuitry phenotype and [Aim 3] synaptic protein expression and cortical cell type-specific gene expression (transcriptomics). Aim 1 will evaluate early post-natal behaviors; cognition anxietydepressive-like and sensorimotor gating in young adult; and social behaviors in adult offspring. In Aim 2 corticaland hippocampal synaptic physiology and cortical connectivity will be evaluated by electrophysiology and laserscanning photostimulation and aligned with quantitative neuronal morphology. In Aim 3 western blotquantification of synaptic proteins and cell type-specific transcriptomics inform circuit development and moleculartrajectories. Impact: Successful completion of the proposed studies will provide the first proof-of-concept thatconsequences of TBI during pregnancy often resulting from IPV can distort developing brain circuity anddetermine a neurodevelopmental disorder behavioral phenotype.