Lombardo, J;
(2013)
Seizure-induced alteration of Ih properties and its impact on CA1 pyramidal neuron excitability.
Doctoral thesis , UCL (University College London).
Abstract
Epilepsy is a neurological disorder characterized by abnormal neuronal excitability which has been suggested to result from altered ion channel activity. Of particular interest are the hyperpolarization-activated cation (HCN) channels which have recently been shown to play an important role in temporal lobe epilepsy (TLE) development. To evaluate how HCN channels are modulated during TLE development, I obtained acute hippocampal slices from appropriate control and “epileptic” rats and recorded the hyperpolarization-activated cation current (Ih) from CA1 pyramidal neurons. My results showed that Ih was enhanced 24 hours after seizure-induction compared to controls but this effect was diminished 1week later. However, in chronically epileptic rats that had started to experience spontaneous seizures Ih was significantly reduced compared to controls, and the excitability of CA1 pyramidal neurons was profoundly increased. To elucidate whether Ih modulation per se affects CA1 pyramidal neuron excitability, I used a recently published conductance-based model of a reconstructed CA1 pyramidal neuron which I adapted to match my experimental conditions. My simulations showed that modifications in Ih influences CA1 pyramidal neuron excitability consistent with that observed in “epileptic” neurons. The simulations also suggested that alteration in other currents, such as the persistent sodium current, together with the reduction of Ih, is required to determine the hyperexcitability of CA1 pyramidal neurons from chronically epileptic rats. In conclusion, Ih can be differentially modulated in CA1 pyramidal neurons during TLE development. These changes are likely to significantly affect CA1 pyramidal cell excitability and may contribute to the process of epileptogenesis.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | Seizure-induced alteration of Ih properties and its impact on CA1 pyramidal neuron excitability |
| Language: | English |
| Keywords: | hyperpolarization-activated current, epilepsy, kainic acid model, CA1 pyramidal neuron |
| UCL classification: | UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1397878 |
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