Post-stroke epileptogenesis is associated with altered intrinsic properties of hippocampal pyramidal neurons leading to increased theta resonance
| Autor: | Kristina Lippmann, Jorge Vera |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Hippocampus Pyramidal cell Neurosciences. Biological psychiatry. Neuropsychiatry BBB dysfunction Hippocampal formation Epileptogenesis Rats Sprague-Dawley 03 medical and health sciences Epilepsy 0302 clinical medicine Seizures M current medicine Animals Theta Rhythm Membrane potential Theta oscillations Chemistry Pyramidal Cells medicine.disease Rats Stroke Electrophysiology 030104 developmental biology medicine.anatomical_structure Theta resonance Neurology Neuroscience 030217 neurology & neurosurgery RC321-571 |
| Zdroj: | Neurobiology of Disease, Vol 156, Iss, Pp 105425-(2021) |
| Popis: | Brain insults like stroke, trauma or infections often lead to blood-brain barrier-dysfunction (BBBd) frequently resulting into epileptogenesis. Affected patients suffer from seizures and cognitive comorbidities that are potentially linked to altered network oscillations. It has been shown that a hippocampal BBBd in rats leads to in vivo seizures and increased power at theta (3–8 Hz), an important type of network oscillations. However, the underlying cellular mechanisms remain poorly understood. At membrane potentials close to the threshold for action potentials (APs) a subpopulation of CA1 pyramidal cells (PCs) displays intrinsic resonant properties due to an interplay of the muscarine-sensitive K+-current (IM) and the persistent Na+-current (INaP). Such resonant neurons are more excitable and generate more APs when stimulated at theta frequencies, being strong candidates for contributing to hippocampal theta oscillations during epileptogenesis. We tested this hypothesis by characterizing changes in intrinsic properties of hippocampal PCs one week after post-stroke epileptogenesis, a model associated with BBBd, using slice electrophysiology and computer modeling. We find a higher proportion of resonant neurons in BBBd compared to sham animals (47 vs. 29%), accompanied by an increase in their excitability. In contrast, BBBd non-resonant neurons showed a reduced excitability, presented with lower impedance and more positive AP threshold. We identify an increase in IM combined with either a reduction in INaP or an increase in ILeak as possible mechanisms underlying the observed changes. Our results support the hypothesis that a higher proportion of more excitable resonant neurons in the hippocampus contributes to increased theta oscillations and an increased likelihood of seizures in a model of post-stroke epileptogenesis. |
| Databáze: | OpenAIRE |
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