The key factor leading to epileptic seizures in rats has been identified by Russian scientists who investigated the complex interaction of neural signals.

The scientists studied the complex changes in the temporal lobe cortex of a rat brain during prolonged epileptic seizes to identify the key factor leading to the seizures. The work has been published in Frontiers in Cellular Neuroscience.

Epistatus is the condition where a person subject to epilepsy experiences seizures which follow each other after a short time. The condition is considered to be particularly dangerous. Although scientists know that this is caused by an excessive excitation of neurons in the brain, the reason for such neuron activity is unclear.

The difficulty of analysing individual neuron signals

Anton Chizhov is a doctor of physical and mathematical sciences, senior researcher at the Ioffe Institute of RAS, and Leading Researcher at Sechenov Institute of Evolutionary Physiology and Biochemistry. Chizhov explained:”Neurons send each other signals that can be excitatory or inhibitory, depending on the type of target receptor on the cell membrane. For example, the first are those that react to glutamate and its analogues, the second are sensitive to gamma-aminobutyric acid or GABA. Yet GABA receptors of those suffering with the epilepsy also become exciting. There lies the main research difficulty: when several signals act on the neuron at once it is very difficult to assess their individual contribution.”

The key mechanism causing epileptic seizures

The researchers investigated the signalling processes in the cortex of the temporal lobe before and after the rat epileptic seizures. They examined the effect of amino acids on receptors of all major types. They found that each of the components of the signal after epileptic electrical discharges becomes stronger and longer.

In order to find out what happened as a result of affecting only one amplified signal on the remaining paths, the team created a mathematical model of interacting nerve cells system.

The results showed that only the conductivity of the AMPA receptors in the network of neurons significantly changes. This leads to stronger excitation of all neurons and stronger synaptic signals recorded on one nerve cell. Chizhov added: “Further studies showed that this is the mechanism of synaptic plasticity with the incorporation of new calcium-permeable AMPA receptors into the cell membranes. Under normal conditions, such a process in the brain is associated with memory and learning, but under pathological conditions it leads to an excitability increase up to tens of minutes. Therefore, the risk of a new convulsive discharge rises, which may lead to pathology fixation.”

Chizhov concluded: “Knowing that embedding calcium-permeable AMPA receptors leads to the consolidation of seizure activity, we can develop new antiepileptic drugs.”