Dynamic Emergence of Neuronal Synchrony During Kindling

The hippocampus is involved in the generation and propagation of epileptic seizures. Although it has been stated that seizures are hypersynchronized activity of neurons, some studies showed desynchronization during seizure onsets. Most of the previous studies were conducted in brain slices. However, the structure of synchronization and propagation during hippocampal seizures in vivo is still undeveloped.

The purpose of this dissertation was to understand the dynamic properties of neuronal firing and quantify the synchrony of high frequency firing in both anesthetized and awake rats during epileptogenesis. A high-speed dynamic recording apparatus was constructed with a microelectrode array to record electrically evoked seizures. We found that as the epileptogenesis progresses, firing of neurons in CA1 region become more synchronized and the propagation is along the lamellar axis in CA1, but not the septotemporal axis. The synchrony of neurons was measured by using the following methods: cross correlation, theta phase synchronization and event synchronization. Cross correlation revealed that the firing pattern was highly correlated during evoked seizures along the lamellar axis but not the septotemporal. Both theta phase synchronization and event synchronization demonstrated that neuronal synchrony increased along the lamellar axis of CA1 pyramidal neurons as kindling progressed, while synchrony along the septotemporal axis remained at a relatively low level. Additionally, the theta phase distribution demonstrated that the firings of CA1 pyramidal cells became preferential for the negative peak of the theta oscillations as the seizure progresses. This was only true in the lamellar direction. Lastly, event synchronization shows that neuronal firings along the lamellar axis were more synchronized than those along the septotemporal axis.

The effects of two commonly prescribed antiepileptic drugs, phenytoin and levetiracetam, on seizure activity and neuronal synchronization in the electrically kindled model were examined. There was a marked decrease in synchronization and propagation after treatment with both phenytoin and levetiracetam. The preferred firing phase, which is around the negative peak of theta oscillation, was lost after both drug treatments.

In this dissertation, we discovered the temporal relationship between the structure of synchrony in CA1 and seizure severity. It can be used to help design a new deep brain stimulation algorithm to interrupt synchrony during epileptogenesis.