Giant Depolarizing Potentials Trigger Transient Changes in the Intracellular Cl- Concentration in CA3 Pyramidal Neurons of the Immature Mouse Hippocampus
Giant depolarizing potentials (GDPs) represent a typical spontaneous activity pattern in the immature hippocampus. GDPs are mediated by GABAergic and glutamatergic synaptic inputs and their initiation requires an excitatory GABAergic action, which is typical for immature neurons due to their elevate...
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2018.00420/full |
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| author | Aniello Lombardi Peter Jedlicka Peter Jedlicka Heiko J. Luhmann Werner Kilb |
| author_facet | Aniello Lombardi Peter Jedlicka Peter Jedlicka Heiko J. Luhmann Werner Kilb |
| author_sort | Aniello Lombardi |
| collection | DOAJ |
| description | Giant depolarizing potentials (GDPs) represent a typical spontaneous activity pattern in the immature hippocampus. GDPs are mediated by GABAergic and glutamatergic synaptic inputs and their initiation requires an excitatory GABAergic action, which is typical for immature neurons due to their elevated intracellular Cl- concentration ([Cl-]i). Because GABAA receptors are ligand-gated Cl- channels, activation of these receptors can potentially influence [Cl-]i. However, whether the GABAergic activity during GDPs influences [Cl-]i is unclear. To address this question we performed whole-cell and gramicidin-perforated patch-clamp recordings from visually identified CA3 pyramidal neurons in immature hippocampal slices of mice at postnatal days 4–7. These experiments revealed that the [Cl-]i of CA3 neurons displays a considerable heterogeneity, ranging from 13 to 70 mM (average 38.1 ± 3.2 mM, n = 36). In accordance with this diverse [Cl-]i, GDPs induced either Cl--effluxes or Cl--influxes. In high [Cl-]i neurons with a negative Cl--driving force (DFCl) the [Cl-]i decreased after a GDP by 12.4 ± 3.4 mM (n = 10), while in low [Cl-]i neurons with a positive DFCl [Cl-]i increased by 4.4 ± 0.9 mM (n = 6). Inhibition of GDP activity by application of the AMPA receptor antagonist CNQX led to a [Cl-]i decrease to 24.7 ± 2.9 mM (n = 8). We conclude from these results, that Cl--fluxes via GABAA receptors during GDPs induced substantial [Cl-]i changes and that this activity-dependent ionic plasticity in neuronal [Cl-]i contributes to the functional consequences of GABAergic responses, emphasizing the concept that [Cl-]i is a state- and compartment-dependent parameter of individual cells. |
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| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-23T10:41:34Z |
| publishDate | 2018-11-01 |
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| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-d57b4991be5a4545b8509b6d817f111b2022-12-21T17:50:09ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-11-011210.3389/fncel.2018.00420420194Giant Depolarizing Potentials Trigger Transient Changes in the Intracellular Cl- Concentration in CA3 Pyramidal Neurons of the Immature Mouse HippocampusAniello Lombardi0Peter Jedlicka1Peter Jedlicka2Heiko J. Luhmann3Werner Kilb4Institute of Physiology, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, GermanyInterdisciplinary Centre for 3Rs in Animal Research, Faculty of Medicine, Justus Liebig University Giessen, Giessen, GermanyInstitute of Clinical Neuroanatomy, Neuroscience Center, Goethe University Frankfurt, Frankfurt, GermanyInstitute of Physiology, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, GermanyInstitute of Physiology, University Medical Center Mainz, Johannes Gutenberg University Mainz, Mainz, GermanyGiant depolarizing potentials (GDPs) represent a typical spontaneous activity pattern in the immature hippocampus. GDPs are mediated by GABAergic and glutamatergic synaptic inputs and their initiation requires an excitatory GABAergic action, which is typical for immature neurons due to their elevated intracellular Cl- concentration ([Cl-]i). Because GABAA receptors are ligand-gated Cl- channels, activation of these receptors can potentially influence [Cl-]i. However, whether the GABAergic activity during GDPs influences [Cl-]i is unclear. To address this question we performed whole-cell and gramicidin-perforated patch-clamp recordings from visually identified CA3 pyramidal neurons in immature hippocampal slices of mice at postnatal days 4–7. These experiments revealed that the [Cl-]i of CA3 neurons displays a considerable heterogeneity, ranging from 13 to 70 mM (average 38.1 ± 3.2 mM, n = 36). In accordance with this diverse [Cl-]i, GDPs induced either Cl--effluxes or Cl--influxes. In high [Cl-]i neurons with a negative Cl--driving force (DFCl) the [Cl-]i decreased after a GDP by 12.4 ± 3.4 mM (n = 10), while in low [Cl-]i neurons with a positive DFCl [Cl-]i increased by 4.4 ± 0.9 mM (n = 6). Inhibition of GDP activity by application of the AMPA receptor antagonist CNQX led to a [Cl-]i decrease to 24.7 ± 2.9 mM (n = 8). We conclude from these results, that Cl--fluxes via GABAA receptors during GDPs induced substantial [Cl-]i changes and that this activity-dependent ionic plasticity in neuronal [Cl-]i contributes to the functional consequences of GABAergic responses, emphasizing the concept that [Cl-]i is a state- and compartment-dependent parameter of individual cells.https://www.frontiersin.org/article/10.3389/fncel.2018.00420/fulldevelopmentCl- homeostasisgramicidin-perforated patch-clamppost-synaptic currentsionic plasticityGABA(A) receptors |
| spellingShingle | Aniello Lombardi Peter Jedlicka Peter Jedlicka Heiko J. Luhmann Werner Kilb Giant Depolarizing Potentials Trigger Transient Changes in the Intracellular Cl- Concentration in CA3 Pyramidal Neurons of the Immature Mouse Hippocampus Frontiers in Cellular Neuroscience development Cl- homeostasis gramicidin-perforated patch-clamp post-synaptic currents ionic plasticity GABA(A) receptors |
| title | Giant Depolarizing Potentials Trigger Transient Changes in the Intracellular Cl- Concentration in CA3 Pyramidal Neurons of the Immature Mouse Hippocampus |
| title_full | Giant Depolarizing Potentials Trigger Transient Changes in the Intracellular Cl- Concentration in CA3 Pyramidal Neurons of the Immature Mouse Hippocampus |
| title_fullStr | Giant Depolarizing Potentials Trigger Transient Changes in the Intracellular Cl- Concentration in CA3 Pyramidal Neurons of the Immature Mouse Hippocampus |
| title_full_unstemmed | Giant Depolarizing Potentials Trigger Transient Changes in the Intracellular Cl- Concentration in CA3 Pyramidal Neurons of the Immature Mouse Hippocampus |
| title_short | Giant Depolarizing Potentials Trigger Transient Changes in the Intracellular Cl- Concentration in CA3 Pyramidal Neurons of the Immature Mouse Hippocampus |
| title_sort | giant depolarizing potentials trigger transient changes in the intracellular cl concentration in ca3 pyramidal neurons of the immature mouse hippocampus |
| topic | development Cl- homeostasis gramicidin-perforated patch-clamp post-synaptic currents ionic plasticity GABA(A) receptors |
| url | https://www.frontiersin.org/article/10.3389/fncel.2018.00420/full |
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