Key Metabolic Enzymes Underlying Astrocytic Upregulation of GABAergic Plasticity
GABAergic plasticity is recognized as a key mechanism of shaping the activity of the neuronal networks. However, its description is challenging because of numerous neuron-specific mechanisms. In particular, while essential role of glial cells in the excitatory plasticity is well established, their i...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2017-05-01
|
| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fncel.2017.00144/full |
| _version_ | 1819173966529429504 |
|---|---|
| author | Przemysław T. Kaczor Jerzy W. Mozrzymas Jerzy W. Mozrzymas |
| author_facet | Przemysław T. Kaczor Jerzy W. Mozrzymas Jerzy W. Mozrzymas |
| author_sort | Przemysław T. Kaczor |
| collection | DOAJ |
| description | GABAergic plasticity is recognized as a key mechanism of shaping the activity of the neuronal networks. However, its description is challenging because of numerous neuron-specific mechanisms. In particular, while essential role of glial cells in the excitatory plasticity is well established, their involvement in GABAergic plasticity only starts to emerge. To address this problem, we used two models: neuronal cell culture (NC) and astrocyte-neuronal co-culture (ANCC), where we chemically induced long-term potentiation at inhibitory synapses (iLTP). iLTP could be induced both in NC and ANCC but in ANCC its extent was larger. Importantly, this functional iLTP manifestation was accompanied by an increase in gephyrin puncta size. Furthermore, blocking astrocyte Krebs cycle with fluoroacetate (FA) in ANCC prevented enhancement of both mIPSC amplitude and gephyrin puncta size but this effect was not observed in NC, indicating a key role in neuron-astrocyte cross-talk. Blockade of monocarboxylate transport with α-Cyano-4-hydroxycinnamic acid (4CIN) abolished iLTP both in NC and ANCC and in the latter model prevented also enlargement of gephyrin puncta. Similarly, blockade of glycogen phosphorylase with BAYU6751 prevented enlargement of gephyrin puncta upon iLTP induction. Finally, block of glutamine synthetase with methionine sulfoxide (MSO) nearly abolished mIPSC increase in both NMDA stimulated cell groups but did not prevent enlargement of gephyrin puncta. In conclusion, we provide further evidence that GABAergic plasticity is strongly regulated by astrocytes and the underlying mechanisms involve key metabolic enzymes. Considering the strategic role of GABAergic interneurons, the plasticity described here indicates possible mechanism whereby metabolism regulates the network activity. |
| first_indexed | 2024-12-22T20:31:28Z |
| format | Article |
| id | doaj.art-9bca13ac9cc84e3996937d758e942d8e |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-22T20:31:28Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-9bca13ac9cc84e3996937d758e942d8e2022-12-21T18:13:36ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022017-05-011110.3389/fncel.2017.00144263954Key Metabolic Enzymes Underlying Astrocytic Upregulation of GABAergic PlasticityPrzemysław T. Kaczor0Jerzy W. Mozrzymas1Jerzy W. Mozrzymas2Department of Molecular Physiology and Neurobiology, Faculty of Biological Sciences, University of WrocławWrocław, PolandDepartment of Molecular Physiology and Neurobiology, Faculty of Biological Sciences, University of WrocławWrocław, PolandLaboratory of Neuroscience, Department of Biophysics, Wrocław Medical UniversityWrocław, PolandGABAergic plasticity is recognized as a key mechanism of shaping the activity of the neuronal networks. However, its description is challenging because of numerous neuron-specific mechanisms. In particular, while essential role of glial cells in the excitatory plasticity is well established, their involvement in GABAergic plasticity only starts to emerge. To address this problem, we used two models: neuronal cell culture (NC) and astrocyte-neuronal co-culture (ANCC), where we chemically induced long-term potentiation at inhibitory synapses (iLTP). iLTP could be induced both in NC and ANCC but in ANCC its extent was larger. Importantly, this functional iLTP manifestation was accompanied by an increase in gephyrin puncta size. Furthermore, blocking astrocyte Krebs cycle with fluoroacetate (FA) in ANCC prevented enhancement of both mIPSC amplitude and gephyrin puncta size but this effect was not observed in NC, indicating a key role in neuron-astrocyte cross-talk. Blockade of monocarboxylate transport with α-Cyano-4-hydroxycinnamic acid (4CIN) abolished iLTP both in NC and ANCC and in the latter model prevented also enlargement of gephyrin puncta. Similarly, blockade of glycogen phosphorylase with BAYU6751 prevented enlargement of gephyrin puncta upon iLTP induction. Finally, block of glutamine synthetase with methionine sulfoxide (MSO) nearly abolished mIPSC increase in both NMDA stimulated cell groups but did not prevent enlargement of gephyrin puncta. In conclusion, we provide further evidence that GABAergic plasticity is strongly regulated by astrocytes and the underlying mechanisms involve key metabolic enzymes. Considering the strategic role of GABAergic interneurons, the plasticity described here indicates possible mechanism whereby metabolism regulates the network activity.http://journal.frontiersin.org/article/10.3389/fncel.2017.00144/fullmetabolisminhibitory long term potentiationminiature inhibitory synaptic currentsmonocarboxylate transporthippocampal neuronsastrocytes |
| spellingShingle | Przemysław T. Kaczor Jerzy W. Mozrzymas Jerzy W. Mozrzymas Key Metabolic Enzymes Underlying Astrocytic Upregulation of GABAergic Plasticity Frontiers in Cellular Neuroscience metabolism inhibitory long term potentiation miniature inhibitory synaptic currents monocarboxylate transport hippocampal neurons astrocytes |
| title | Key Metabolic Enzymes Underlying Astrocytic Upregulation of GABAergic Plasticity |
| title_full | Key Metabolic Enzymes Underlying Astrocytic Upregulation of GABAergic Plasticity |
| title_fullStr | Key Metabolic Enzymes Underlying Astrocytic Upregulation of GABAergic Plasticity |
| title_full_unstemmed | Key Metabolic Enzymes Underlying Astrocytic Upregulation of GABAergic Plasticity |
| title_short | Key Metabolic Enzymes Underlying Astrocytic Upregulation of GABAergic Plasticity |
| title_sort | key metabolic enzymes underlying astrocytic upregulation of gabaergic plasticity |
| topic | metabolism inhibitory long term potentiation miniature inhibitory synaptic currents monocarboxylate transport hippocampal neurons astrocytes |
| url | http://journal.frontiersin.org/article/10.3389/fncel.2017.00144/full |
| work_keys_str_mv | AT przemysławtkaczor keymetabolicenzymesunderlyingastrocyticupregulationofgabaergicplasticity AT jerzywmozrzymas keymetabolicenzymesunderlyingastrocyticupregulationofgabaergicplasticity AT jerzywmozrzymas keymetabolicenzymesunderlyingastrocyticupregulationofgabaergicplasticity |