A.Yu. Buchin, G. Huberfeld, R. Miles, A. V. Chizhov, B.S. Gutkin, V. Petrov
Price: 50 руб.
Experimentally it has been found that around 20% of pyramidal cells in epileptogenic human subiculum do not have KCC2 co-transporter. This pathology leads to the increased chloride level in pyramidal cells, what changes the action of GABA synapses from inhibition to excitation. In this work we propose the single neuron biophysical model to explain the mechanisms of this pathology. We show that decreasing the activity of the KCC2 brings the cell to the continuous spiking regime associated with
the seizure activity. Using a set of simplifi cations we show the minimal biophysical model capable of describing this effect. The model proposed in this work provides the explanation for KCC2 pathology in pyramidal cells found in the temporal lobe.
Keywords: epilepsy, KCC2, extracellular potassium, intracellular chloride.
REFERENCES
1. Beghi, E., Berg, A., Carpio, A., Forsgren, L., Hesdorffer, D.C., Hauser, W.A.,
Malmgren, K, Shinnar, S., Temkin, N., Thurman, D., & Tomson, T. Comment on
epileptic seizures and epilepsy: definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE). Epilepsia, 2005, 46(10), 1698–1699.
2. Huberfeld, G., Wittner, L., Clemenceau, S., Baulac, M., Kaila, K., Miles, R., &
Rivera, C. Perturbed chloride homeostasis and GABAergic signaling in human temporal
lobe epilepsy. The Journal of neuroscience, 2007, 27(37), 9866–9873.
3. Buchin, A., Chizhov, A., Huberfeld, G., Miles, R., & Gutkin, B. (in press) Reduced
efficacy of the KCC2 co-transporter promotes epileptic oscillations in subiculum
network model. Journal of Neuroscience.
4. Jedlicka, P., Deller, T., Gutkin, B.S., & Backus, K.H. Activity-dependent
intracellular chloride accumulation and diffusion controls GABA(A) receptor-mediated
synaptic transmission. Hippocampus, 2011, 21(8), 885–898.
5. Khalilov, I., Dzhala, V., Ben-Ari, Y., & Khazipov, R. Dual role of GABA in the
neonatal rat hippocampus. Developmental neuroscience, 1999, 21(3–5), 310–319.
6. Rivera, C., Voipio, J., Payne, J.A., Ruusuvuori, E., Lahtinen, H., Lamsa, K.,
Privola, U., Saarma, M., & Kaila, K. The K+/Cl− co-transporter KCC2 renders GABA
hyperpolarizing during neuronal maturation. Nature, 1999, 397(6716), 251–255.
7. Krishnan, G.P., & Bazhenov, M. Ionic dynamics mediate spontaneous termination
of seizures and postictal depression state. The Journal of Neuroscience, 2011, 31(24),
8870–8882.
8. Bazhenov, M., Timofeev, I., Steriade, M., & Sejnowski, T.J. Potassium model for
slow (2–3 Hz) in vivo neocortical paroxysmal oscillations. Journal of neurophysiology,
2004, 92(2), 1116–1132.
9. Mainen, Z.F., & Sejnowski, T.J. Influence of dendritic structure on firing pattern
in model neocortical neurons. Nature, 1996, 382(6589), 363–366.
10. Chizhov, A.V. Conductance-based refractory density model of primary visual
cortex. Journal of computational neuroscience, 2014, 36(2), 297–319.
11. Blaesse, P., Airaksinen, M.S., Rivera, C., & Kaila, K. Cation-chloride
cotransporters and neuronal function. Neuron, 2009, 61(6), 820–838.
12. Chizhov, A.V. A model for evoked activity of hippocampal neuronal population.
Biophysics, 2002, 47(6), 1086–1094.
13. Huberfeld, G., de la Prida, L.M., Pallud, J., Cohen, I., Le Van Quyen, M.,
Adam, C., Clemenceau, S., Baulac, M., & Miles, R. Glutamatergic pre-ictal discharges
emerge at the transition to seizure in human epilepsy. Nature neuroscience, 2011, 14(5), 627–634.
