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Autism Spectrum Disorder (ASD; autism) is a neurodevelopmental disorder characterised by deficits in social communication, and restricted and/or repetitive behaviours. While the precise pathophysiologies are unclear, increasing evidence supports a role for dysregulated neuroinflammation in the brain with potential effects on synapse function. Here, we studied characteristics of microglia and astrocytes in the Neuroligin-3 (NL3 R451C) mouse model of autism since these cell types are involved in regulating both immune and synapse function. We observed increased microglial density in the dentate gyrus (DG) of NL3 R451C mice without morphological differences. In contrast, WT and NL3 R451C mice had similar astrocyte density but astrocyte branch length, the number of branch points, as well as cell radius and area were reduced in the DG of NL3 R451C mice. Because retraction of astrocytic processes has been linked to altered synaptic transmission and dendrite formation, we assessed for regional changes in pre-and postsynaptic protein expression in the cortex, striatum and cerebellum in NL3 R451C mice. NL3 R451C mice showed increased striatal postsynaptic density 95 (PSD-95) protein levels and decreased cortical expression of synaptosomal-associated protein 25 (SNAP-25). These changes could contribute to dysregulated neurotransmission and cognition deficits previously reported in these mice. Autism Spectrum Disorder (ASD; autism) is a neurodevelopmental disorder estimated to affect 1 in 54 children 1. Autism is characterised by deficits in social communication, and restricted and/or repetitive patterns of behaviour 2. A complex interaction between genetic and environmental factors is thought to contribute to autism. The clinical heterogeneity and variability in presentation and severity of autism has made diagnosis, treatment and the study of autism-relevant neurobiology challenging 3. However, functional and neuroanatomical abnormalities are consistently reported in autism patients 4-6 , with increasing evidence supporting a role for neuroinflammation in autism pathophysiology 7-9. Neuroinflammation involves the sustained, and often unwarranted, increase in activity of glial cells (i.e. microglia and astrocytes), which release many pro-inflammatory cytokines and chemokines in response to injury, infection or disease. During this activity, 'reactive' microglia and astrocytes show altered morphology. Aberrant neuroimmune profiles have been documented in autism including increased densities of reactive microglia and astrocytes in several brain regions 10-12 accompanied by alterations in cytokine and chemokine secretion in brain tissue 10,13 , cerebrospinal fluid 10,14 and blood 15-17 of autism patients compared to neurotypical controls. In addition to regulating immune function, microglia and astrocytes assist in maintaining synaptic function. Abnormal glial function may therefore influence synaptic circuitry and neuronal connectivity within the central nervous system (CNS) and contribute to regional-specific under-connecti...

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