The membrane origin of epileptic‑related paroxysms: numerical experiments to model the transition from a pacemaker potential to paroxysmal depolarization shifts in the absence of synaptic inputs
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| Autores: | , |
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| 格式: | artículo de revisión |
| Fecha de Publicación: | 2025 |
| 實物特徵: | Paroxysmal depolarization shift (PDS) has been widely recognized as a characteristic feature of epileptic activity. The PDS is typically interpreted as a giant excitatory potential resulting from enhanced synaptic transmission, aligning with the prevailing understanding of epilepsy as a network mechanism that involves alterations in the balance of synaptic activity towards increased excitation. Several papers reported PDS recordings from single-cell snail neurons, and it has been hypothesized that PDS originates from abnormal pacemaker potentials. A physiologically inspired mathematical model was used to assess this hypothesis and examine the transition from a pacemaker potential to a PDS. By modifying several parameters in a first oscillation model, we demonstrated that it is possible to transition from fast, low-amplitude oscillations to slow, high-amplitude oscillations. Additionally, by smoothly adjusting specific biophysical parameters of the model, we could generate, long-lasting depolarizations resembling PDS in a bifurcation-like scenario. Notably, adding to this simplified model a spike-generating mechanism, former membrane biophysical changes evoked transitions from action potentials to doublets and PDS of increasing duration, as observed in single-cell recordings during dug-induced epileptic-like activity. Overall, our numerical experiments support the concept of pacemaker potential transitioning into the electrical characteristics of epileptic-like activity and suggest a potential scenario for this transition in the absence of synaptic inputs. |
| País: | Kérwá |
| 機構: | Universidad de Costa Rica |
| Repositorio: | Kérwá |
| 語言: | Inglés |
| OAI Identifier: | oai:kerwa.ucr.ac.cr:10669/101803 |
| 在線閱讀: | https://hdl.handle.net/10669/101803 https://doi.org/10.1007/s12551-025-01284-z |
| Palabra clave: | epilepsy paroxysm PDS invertebrate neuron mathematical modeling pacemaker potential |