Post-stroke epileptogenesis is associated with altered intrinsic properties of hippocampal pyramidal neurons leading to increased theta resonance

NEUROBIOLOGY OF DISEASE

卷:156

Article

Vera, Jorge^1,2  Lippmann, Kristina^1,3 

[1] Marine Biol Lab, Grass Lab, Woods Hole, MA 02543 USA

[2] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Woods Hole, MA 02543 USA

[3] Univ Leipzig, Med Fac, Carl Ludwig Inst Physiol, Liebigstr 27a, D-04103 Leipzig, Germany

关键词: Theta resonance;    Theta oscillations;    Hippocampus;    Pyramidal cell;    BBB dysfunction;    Epilepsy;    Persistent sodium current;    M current;    Impedance;   

DOI  :  10.1016/j.nbd.2021.105425

来源: Elsevier

【 摘 要 】

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.