Depolarization and Hyperexcitability of Cortical Motor Neurons after Spinal Cord Injury Associates with Reduced HCN Channel Activity.
Bruno BenedettiLara BielerChristina Erhardt-KreutzerDominika JakubecovaAriane BenedettiMaximilian ReisingerDominik DannehlChristian ThomeMaren EngelhardtSebastien Couillard-DespresPublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- spinal cord injury
- spinal cord
- neuropathic pain
- healthcare
- palliative care
- randomized controlled trial
- transcranial direct current stimulation
- liver failure
- clinical trial
- chronic pain
- blood brain barrier
- study protocol
- acute respiratory distress syndrome
- respiratory failure
- cell cycle arrest
- optical coherence tomography
- aortic dissection