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 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.
Verfasserangaben: | Aniello LombardiORCiDGND, Peter JedličkaORCiDGND, Heiko LuhmannORCiDGND, Werner KilbORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-627057 |
DOI: | https://doi.org/10.1371/journal.pcbi.1008573 |
ISSN: | 1553-7358 |
Titel des übergeordneten Werkes (Englisch): | PLoS Computational Biology |
Verlag: | Public Library of Science |
Verlagsort: | San Francisco, Calif. |
Dokumentart: | Wissenschaftlicher Artikel |
Sprache: | Englisch |
Datum der Veröffentlichung (online): | 19.01.2021 |
Datum der Erstveröffentlichung: | 19.01.2021 |
Veröffentlichende Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Datum der Freischaltung: | 06.09.2023 |
Freies Schlagwort / Tag: | Depolarization; Gamma-aminobutyric acid; Neuronal dendrites; Neuronal morphology; Neuronal plasticity; Neurons; Receptor physiology; Synapses |
Jahrgang: | 17 |
Ausgabe / Heft: | 1, art. e1008573 |
Aufsatznummer: | e1008573 |
Seitenzahl: | 25 |
Erste Seite: | 1 |
Letzte Seite: | 25 |
Bemerkung: | Data Availability: The source code of all models and stimulation files used in the present paper can be found in ModelDB (http://modeldb.yale.edu/266823). |
HeBIS-PPN: | 512610339 |
Institute: | Medizin / Medizin |
Wissenschaftliche Zentren und koordinierte Programme / Frankfurt Institute for Advanced Studies (FIAS) | |
DDC-Klassifikation: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Lizenz (Deutsch): | Creative Commons - CC BY - Namensnennung 4.0 International |