Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons.
The impact of GABAergic transmission on neuronal excitability depends on the Cl--gradient across membranes. However, the Cl--fluxes through GABAA receptors alter the intracellular Cl- concentration ([Cl-]i) and in turn attenuate GABAergic responses, a process termed ionic plasticity. Recently it has...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1008573 |
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| author | Aniello Lombardi Peter Jedlicka Heiko J Luhmann Werner Kilb |
| author_facet | Aniello Lombardi Peter Jedlicka Heiko J Luhmann Werner Kilb |
| author_sort | Aniello Lombardi |
| collection | DOAJ |
| description | The impact of GABAergic transmission on neuronal excitability depends on the Cl--gradient across membranes. However, the Cl--fluxes through GABAA receptors alter the intracellular Cl- concentration ([Cl-]i) and in turn attenuate GABAergic responses, a process termed ionic plasticity. Recently it has been shown that coincident glutamatergic inputs significantly affect ionic plasticity. Yet how the [Cl-]i changes depend on the properties of glutamatergic inputs and their spatiotemporal relation to GABAergic stimuli is unknown. To investigate this issue, we used compartmental biophysical models of Cl- dynamics simulating either a simple ball-and-stick topology or a reconstructed CA3 neuron. These computational experiments demonstrated that glutamatergic co-stimulation enhances GABA receptor-mediated Cl- influx at low and attenuates or reverses the Cl- efflux at high initial [Cl-]i. The size of glutamatergic influence on GABAergic Cl--fluxes depends on the conductance, decay kinetics, and localization of glutamatergic inputs. Surprisingly, the glutamatergic shift in GABAergic Cl--fluxes is invariant to latencies between GABAergic and glutamatergic inputs over a substantial interval. In agreement with experimental data, simulations in a reconstructed CA3 pyramidal neuron with physiological patterns of correlated activity revealed that coincident glutamatergic synaptic inputs contribute significantly to the activity-dependent [Cl-]i changes. Whereas the influence of spatial correlation between distributed glutamatergic and GABAergic inputs was negligible, their temporal correlation played a significant role. In summary, our results demonstrate that glutamatergic co-stimulation had a substantial impact on ionic plasticity of GABAergic responses, enhancing the attenuation of GABAergic inhibition in the mature nervous systems, but suppressing GABAergic [Cl-]i changes in the immature brain. Therefore, glutamatergic shift in GABAergic Cl--fluxes should be considered as a relevant factor of short-term plasticity. |
| first_indexed | 2024-12-13T17:56:34Z |
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| id | doaj.art-6cc5f0419ebe4e72aaea546755afe831 |
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| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-13T17:56:34Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Computational Biology |
| spelling | doaj.art-6cc5f0419ebe4e72aaea546755afe8312022-12-21T23:36:22ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582021-01-01171e100857310.1371/journal.pcbi.1008573Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons.Aniello LombardiPeter JedlickaHeiko J LuhmannWerner KilbThe impact of GABAergic transmission on neuronal excitability depends on the Cl--gradient across membranes. However, the Cl--fluxes through GABAA receptors alter the intracellular Cl- concentration ([Cl-]i) and in turn attenuate GABAergic responses, a process termed ionic plasticity. Recently it has been shown that coincident glutamatergic inputs significantly affect ionic plasticity. Yet how the [Cl-]i changes depend on the properties of glutamatergic inputs and their spatiotemporal relation to GABAergic stimuli is unknown. To investigate this issue, we used compartmental biophysical models of Cl- dynamics simulating either a simple ball-and-stick topology or a reconstructed CA3 neuron. These computational experiments demonstrated that glutamatergic co-stimulation enhances GABA receptor-mediated Cl- influx at low and attenuates or reverses the Cl- efflux at high initial [Cl-]i. The size of glutamatergic influence on GABAergic Cl--fluxes depends on the conductance, decay kinetics, and localization of glutamatergic inputs. Surprisingly, the glutamatergic shift in GABAergic Cl--fluxes is invariant to latencies between GABAergic and glutamatergic inputs over a substantial interval. In agreement with experimental data, simulations in a reconstructed CA3 pyramidal neuron with physiological patterns of correlated activity revealed that coincident glutamatergic synaptic inputs contribute significantly to the activity-dependent [Cl-]i changes. Whereas the influence of spatial correlation between distributed glutamatergic and GABAergic inputs was negligible, their temporal correlation played a significant role. In summary, our results demonstrate that glutamatergic co-stimulation had a substantial impact on ionic plasticity of GABAergic responses, enhancing the attenuation of GABAergic inhibition in the mature nervous systems, but suppressing GABAergic [Cl-]i changes in the immature brain. Therefore, glutamatergic shift in GABAergic Cl--fluxes should be considered as a relevant factor of short-term plasticity.https://doi.org/10.1371/journal.pcbi.1008573 |
| spellingShingle | Aniello Lombardi Peter Jedlicka Heiko J Luhmann Werner Kilb Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons. PLoS Computational Biology |
| title | Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons. |
| title_full | Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons. |
| title_fullStr | Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons. |
| title_full_unstemmed | Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons. |
| title_short | Coincident glutamatergic depolarizations enhance GABAA receptor-dependent Cl- influx in mature and suppress Cl- efflux in immature neurons. |
| title_sort | coincident glutamatergic depolarizations enhance gabaa receptor dependent cl influx in mature and suppress cl efflux in immature neurons |
| url | https://doi.org/10.1371/journal.pcbi.1008573 |
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