Astrocyte glutamate uptake coordinates experience‐dependent, eye‐specific refinement in developing visual cortex
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,...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022
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| Online Access: | https://hdl.handle.net/1721.1/140404 |
| _version_ | 1826194819178823680 |
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| author | Sipe, Grayson O. Petravicz, Jeremy Rikhye, Rajeev V. Garcia, Rodrigo Mellios, Nikolaos Sur, Mriganka |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Sipe, Grayson O. Petravicz, Jeremy Rikhye, Rajeev V. Garcia, Rodrigo Mellios, Nikolaos Sur, Mriganka |
| author_sort | Sipe, Grayson O. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:02:18Z |
| format | Article |
| id | mit-1721.1/140404 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:02:18Z |
| publishDate | 2022 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1404042024-06-06T19:31:20Z Astrocyte glutamate uptake coordinates experience‐dependent, eye‐specific refinement in developing visual cortex Sipe, Grayson O. Petravicz, Jeremy Rikhye, Rajeev V. Garcia, Rodrigo Mellios, Nikolaos Sur, Mriganka Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory 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. 2022-02-16T15:59:44Z 2022-02-16T15:59:44Z 2021-03-06 Article http://purl.org/eprint/type/JournalArticle 0894-1491 1098-1136 https://hdl.handle.net/1721.1/140404 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. en http://dx.doi.org/10.1002/glia.23987 Glia Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Wiley |
| spellingShingle | Sipe, Grayson O. Petravicz, Jeremy Rikhye, Rajeev V. Garcia, Rodrigo Mellios, Nikolaos Sur, Mriganka Astrocyte glutamate uptake coordinates experience‐dependent, eye‐specific refinement in developing visual cortex |
| title | Astrocyte glutamate uptake coordinates experience‐dependent, eye‐specific refinement in developing visual cortex |
| title_full | Astrocyte glutamate uptake coordinates experience‐dependent, eye‐specific refinement in developing visual cortex |
| title_fullStr | Astrocyte glutamate uptake coordinates experience‐dependent, eye‐specific refinement in developing visual cortex |
| title_full_unstemmed | Astrocyte glutamate uptake coordinates experience‐dependent, eye‐specific refinement in developing visual cortex |
| title_short | Astrocyte glutamate uptake coordinates experience‐dependent, eye‐specific refinement in developing visual cortex |
| title_sort | astrocyte glutamate uptake coordinates experience dependent eye specific refinement in developing visual cortex |
| url | https://hdl.handle.net/1721.1/140404 |
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