Depolarization and hyperexcitability of cortical motor neurons after spinal cord injury associates with reduced HCN channel activity
A spinal cord injury (SCI) damages the axonal projections of neurons residing in the neocortex. This axotomy changes cortical excitability and results in dysfunctional activity and output of infragranular cortical layers. Thus, addressing cortical pathophysiology after SCI will be instrumental in pr...
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| Hauptverfasser: | , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
1 March 2023
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| In: |
International journal of molecular sciences
Year: 2023, Jahrgang: 24, Heft: 5, Pages: 1-14 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms24054715 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms24054715 Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/24/5/4715 
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| Verfasserangaben: | Bruno Benedetti, Lara Bieler, Christina Erhardt-Kreutzer, Dominika Jakubecova, Ariane Benedetti, Maximilian Reisinger, Dominik Dannehl, Christian Thome, Maren Engelhardt and Sebastien Couillard-Despres |
MARC
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| 245 | 1 | 0 | |a Depolarization and hyperexcitability of cortical motor neurons after spinal cord injury associates with reduced HCN channel activity |c Bruno Benedetti, Lara Bieler, Christina Erhardt-Kreutzer, Dominika Jakubecova, Ariane Benedetti, Maximilian Reisinger, Dominik Dannehl, Christian Thome, Maren Engelhardt and Sebastien Couillard-Despres |
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| 520 | |a A spinal cord injury (SCI) damages the axonal projections of neurons residing in the neocortex. This axotomy changes cortical excitability and results in dysfunctional activity and output of infragranular cortical layers. Thus, addressing cortical pathophysiology after SCI will be instrumental in promoting recovery. However, the cellular and molecular mechanisms of cortical dysfunction after SCI are poorly resolved. In this study, we determined that the principal neurons of the primary motor cortex layer V (M1LV), those suffering from axotomy upon SCI, become hyperexcitable following injury. Therefore, we questioned the role of hyperpolarization cyclic nucleotide gated channels (HCN channels) in this context. Patch clamp experiments on axotomized M1LV neurons and acute pharmacological manipulation of HCN channels allowed us to resolve a dysfunctional mechanism controlling intrinsic neuronal excitability one week after SCI. Some axotomized M1LV neurons became excessively depolarized. In those cells, the HCN channels were less active and less relevant to control neuronal excitability because the membrane potential exceeded the window of HCN channel activation. Care should be taken when manipulating HCN channels pharmacologically after SCI. Even though the dysfunction of HCN channels partakes in the pathophysiology of axotomized M1LV neurons, their dysfunctional contribution varies remarkably between neurons and combines with other pathophysiological mechanisms. | ||
| 650 | 4 | |a axotomy | |
| 650 | 4 | |a corticospinal tract | |
| 650 | 4 | |a HCN channels | |
| 650 | 4 | |a primary motor cortex | |
| 650 | 4 | |a spinal cord injury | |
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| 700 | 1 | |a Benedetti, Ariane |e VerfasserIn |4 aut | |
| 700 | 1 | |a Reisinger, Maximilian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dannehl, Dominik |d 1994- |e VerfasserIn |0 (DE-588)119681452X |0 (DE-627)167864059X |4 aut | |
| 700 | 1 | |a Thome, Christian |e VerfasserIn |4 aut | |
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| 700 | 1 | |a Couillard-Despres, Sebastien |e VerfasserIn |4 aut | |
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