From IPSPs to EPSPs: Transition to seizures in the mouse hippocampus

Transition to seizures in the isolated immature mouse hippocampus: a switch from dominant phasic inhibition to dominant phasic excitation.
M. Derchansky, S. S. Jahromi, M. Manami, D.S. Shin, A. Sik, and P. L. Carlen

Neuronal networks can display non-linear complex behaviours that result in multiple stable states, with the capacity to undergo spontaneous transition between these states. An in vitro model of temporal lobe epilepsy (TLE) generates recurrent seizure-like events. The authors studied the sequence of inhibitory and excitatory events during the preictal state.

In animal models of epilepsy, dendritic but not somatic GABAergic inhibition is decreased and it has been hypothesized that this is the mechanism responsible for ictal generation.
Anothor hypothesis for ictal generation is that interneurons might be involved in synchronizing large neuronal populatios. This synchronization is possible by their abundant connectivity to pyramidal cells. Excitation might be achieved by the alteration of the intracellular chloride gradient after prolonged high-frequency activation of GABA-A receptor.


During the preictal state, there was a total reversal in the polarity of the synaptic potentials in pyramidal cells, fast-spiking cells, and non-FS cells.

The hyperpolarizing potentials during preictal state are generated by recurrent IPSPs (Cl-).
However, the reversal is not due to the change in the reversal potential for Cl ion. The authors suggest that the excitatory drive was produced by a complex change in the synaptic interactions among pyramidal cells and interneurons.

J. Physiol. 586.2, 477-494 (2008).