Bar, Lior;
Shalom, Lia;
Lezmy, Jonathan;
Peretz, Asher;
Attali, Bernard;
(2022)
Excitatory and inhibitory hippocampal neurons differ in their homeostatic adaptation to chronic M-channel modulation.
Frontiers in Molecular Neuroscience
, 15
, Article 972023. 10.3389/fnmol.2022.972023.
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Abstract
A large body of studies has investigated bidirectional homeostatic plasticity both in vitro and in vivo using numerous pharmacological manipulations of activity or behavioral paradigms. However, these experiments rarely explored in the same cellular system the bidirectionality of the plasticity and simultaneously on excitatory and inhibitory neurons. M-channels are voltage-gated potassium channels that play a crucial role in regulating neuronal excitability and plasticity. In cultured hippocampal excitatory neurons, we previously showed that chronic exposure to the M-channel blocker XE991 leads to adaptative compensations, thereby triggering at different timescales intrinsic and synaptic homeostatic plasticity. This plastic adaptation barely occurs in hippocampal inhibitory neurons. In this study, we examined whether this homeostatic plasticity induced by M-channel inhibition was bidirectional by investigating the acute and chronic effects of the M-channel opener retigabine on hippocampal neuronal excitability. Acute retigabine exposure decreased excitability in both excitatory and inhibitory neurons. Chronic retigabine treatment triggered in excitatory neurons homeostatic adaptation of the threshold current and spontaneous firing rate at a time scale of 4–24 h. These plastic changes were accompanied by a substantial decrease in the M-current density and by a small, though significant, proximal relocation of Kv7.3-FGF14 segment along the axon initial segment. Thus, bidirectional homeostatic changes were observed in excitatory neurons though not symmetric in kinetics and mechanisms. Contrastingly, in inhibitory neurons, the compensatory changes in intrinsic excitability barely occurred after 48 h, while no homeostatic normalization of the spontaneous firing rate was observed. Our results indicate that excitatory and inhibitory hippocampal neurons differ in their adaptation to chronic alterations in neuronal excitability induced by M-channel bidirectional modulation.
| Type: | Article |
|---|---|
| Title: | Excitatory and inhibitory hippocampal neurons differ in their homeostatic adaptation to chronic M-channel modulation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fnmol.2022.972023 |
| Publisher version: | https://doi.org/10.3389/fnmol.2022.972023 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Axon initial segment, homeostatic plasticity, M-channels, potassium channel, synaptic plasticity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10168514 |
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