Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.25.113613v1?rss=1 Authors: Sipe, G. O., Petravicz, J., Rikhye, R., Garcia, R., Mellios, N., Sur, M. Abstract: The uptake of glutamate by astrocytes actively shapes synaptic transmission, however its role in the development and plasticity of neuronal circuits remains poorly understood. The astrocytic glutamate transporter, GLT1 is the predominant source of glutamate clearance in the adult mouse cortex. Here, we examined the structural and functional development of the visual cortex in GLT1 heterozygous (HET) mice using two-photon microscopy, immunohistochemistry and slice electrophysiology. We find that though eye-specific thalamic axonal segregation is intact, binocular refinement in the primary visual cortex is disrupted. Eye-specific responses to visual stimuli in GLT1 HET mice show a failure of binocular matching and abnormally high responses to ipsilateral stimuli resulting in a decreased ocular dominance index and a greater mismatch between preferred orientation to ipsilateral and contralateral eye stimulation. Furthermore, the balance of excitation and inhibition is dysregulated with an increase in somatostatin positive interneurons, decrease in parvalbumin positive interneurons, and increase in dendritic spine density in the basal dendrites of layer 2/3 excitatory neurons. Monocular deprivation induces atypical ocular dominance plasticity in GLT1 HET mice, with an unusual depression of ipsilateral open eye responses; however, this change in ipsilateral responses correlates well with an upregulation of GLT1 protein following monocular deprivation. These results demonstrate that a key function of astrocytic GLT1 function during development is the experience-dependent refinement of ipsilateral eye inputs relative to contralateral eye inputs in visual cortex. Copy rights belong to original authors. Visit the link for more info