Astrocyte glutamate uptake coordinates experience‐dependent, eye‐specific refinement in developing visual cortex
Name
10.1002-glia.23987.pdf
Size
7.41 MB
Format
Adobe PDF
Checksum (MD5)
360a979b796f404c706eb9b3b18ae986
Author(s)
Sipe, Grayson O.
Petravicz, Jeremy
Rikhye, Rajeev V.
Garcia, Rodrigo
Mellios, Nikolaos
Sur, Mriganka
Date Issued
March 6, 2021
Journal
Glia
Publisher
Wiley
Citation
Sipe, GO, Petravicz, J, Rikhye, RV, Garcia, R, Mellios, N, Sur, M. Astrocyte glutamate uptake coordinates experience-dependent, eye-specific refinement in developing visual cortex. Glia. 2021; 69: 1723– 1735.
Version
Author's final manuscript
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 altered binocular matching, with abnormally high responses to ipsilateral compared to contralateral eye stimulation and a greater mismatch between preferred orientation selectivity of ipsilateral and contralateral eye responses. Furthermore, we observe an increase in dendritic spine density in the basal dendrites of layer 2/3 excitatory neurons suggesting aberrant spine pruning. 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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Picower Institute for Learning and Memory
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1002/glia.23987
