Transient cerebral ischemia increases CA1 pyramidal neuron excitability

Yuan Fan, Ping Deng, Yu Chi Wang, Hui Chen Lu, Zao C. Xu, Paul E. Schulz

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Abstract

In human and experimental animals, the hippocampal CA1 region is one of the most vulnerable areas of the brain to ischemia. Pyramidal neurons in this region die 2-3 days after transient cerebral ischemia whereas other neurons in the same region remain intact. The mechanisms underlying the selective and delayed neuronal death are unclear. We tested the hypothesis that there is an increase in post-synaptic intrinsic excitability of CA1 pyramidal neurons after ischemia that exacerbates glutamatergic excitotoxicity. We performed whole-cell patch-clamp recordings in brain slices obtained 24 h after in vivo transient cerebral ischemia. We found that the input resistance and membrane time constant of the CA1 pyramidal neurons were significantly increased after ischemia, indicating an increase in neuronal excitability. This increase was associated with a decrease in voltage sag, suggesting a reduction of the hyperpolarization-activated non-selective cationic current (Ih). Moreover, after blocking Ih with ZD7288, the input resistance of the control neurons increased to that of the post-ischemia neurons, suggesting that a decrease in Ih contributes to increased excitability after ischemia. Finally, when lamotrigine, an enhancer of dendritic Ih, was applied immediately after ischemia, there was a significant attenuation of CA1 cell loss. These data suggest that an increase in CA1 pyramidal neuron excitability after ischemia may exacerbate cell loss. Moreover, this dendritic channelopathy may be amenable to treatment.

Original languageEnglish (US)
Pages (from-to)415-421
Number of pages7
JournalExperimental Neurology
Volume212
Issue number2
DOIs
StatePublished - Aug 1 2008

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ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Fan, Y., Deng, P., Wang, Y. C., Lu, H. C., Xu, Z. C., & Schulz, P. E. (2008). Transient cerebral ischemia increases CA1 pyramidal neuron excitability. Experimental Neurology, 212(2), 415-421. https://doi.org/10.1016/j.expneurol.2008.04.032