The incidence of developmental delays in children is 18% of the US population, with boys outnumbering girls. Environmental factors (e.g. fetal growth deviations and hypoglycemia) and genetic aberrations play etiological roles. Developmental delays and autism spectrum disorders (ASDs) have been associated with copy number variations (CNVs), deletion or duplication of the Slc2A3 gene on chromosome 12. ASDs are life-long neurodevelopmental disorders (NDD) with brain synaptic disconnectivity. Slc2A3 gene translation product, Glut3 protein is the neuronal facilitative glucose transporter that fuels oxidative metabolism necessary for neural cell proliferation and differentiation, synaptic formation/plasticity and function/neurotransmission. The phenotypically distinct human GLUT3 deficiency associated with CNVs is being described in children with the advent of newer genetic technologies. We previously observed that in the classical mono-allelic Slc2A3 deletion mouse with fetal growth restriction (FGR), males expressed ASD symptoms. To separate the impact of FGR on aberrant brain organogenesis and the advent of morbidities, we hypothesize that lack of Glut3 in cerebral cortical and hippocampal neurons will reveal a phenotype ranging from autism to intellectual disability, thereby unraveling possibilities for screening and interventions, that an aid individuals with these presenting features and prevent some NDDs and their associated co-morbidities. To test this hypothesis, we propose the following specific aims by disrupting neuron-specific Slc2A3 in a conditional neuronal glut3 null deletion mouse line (glut3loxP/loxP/nestinCre+), to study the impact on: 1. a. Placental and fetal brain Slc2A3 expression and function at different gestational stages (G13, G19) and b. the role of fetal growth restriction (FGR) on placental and fetal brain Slc2A3 expression and function. 2. Postnatal a. metabolic status which includes plasma, cerebro-spinal fluid and brain (neuronal and glial) metabolic profile with compensatory mechanisms, b. brain morphology and immunohistochemistry to detect different cell types and aberrations in processes. 3. Postnatal and adult a. neurobehavioral phenotype including activity, seizures, cognition, working memory, anxiety, socialization, vocalization and stereotypies, with b. electrophysiology in patch-clamped neurons to detect functional impairments, and possibility of reversal with a ketogenic diet. The results of our proposed studies will inform us about the contribution and impact of glut3 deficiency on ASDs, setting the stage for future endophenotype human studies in detecting glut3 gene variations in the multifactorial ASD/NDDs. This will enable subsequent therapeutic discovery. The insights gained will be generalizable in preventing and treating other conditions related to deficient neuronal glucose supply (e.g. FGR) encountered during early development and resulting in NDDs with clinical features of ASDs, sometimes presenting with EEG seizures and infantile microcephaly.