Synaptic Dysfunction in Epilepsy

Epilepsy is one of the prevalent cerebral diseases, and despite intensive research of this pathology for many years, modern medicine cannot effectively control seizure manifestations in almost a third of patients. In epilepsy, there is a reorganization of neural networks, which is the result of the death of some neurons and the formation of new neuronal connections with altered properties. In this review, we focused on the analysis of changes in the properties of a key element of neural networks, the chemical synapse, immediately after epileptic activity, during epileptogenesis, and in chronic epilepsy. Since the synapse includes not only neuronal pre- and postsynaptic parts, but also glial components, our consideration includes changes in the properties of astrocytes and microglia. Epileptic activity causes numerous modifications in synapse function: changes in the probability of mediator release, the alteration of subunit composition of postsynaptic receptors, impairments of synaptic plasticity, and changes in morphology and activity of astrocytes and microglia. Glial cells release several gliatransmitters and cytokines, which in turn modify synaptic transmission. In some cases, the combination of these changes is favorable and allows compensating almost completely the consequences of epileptic activity for the nervous system. However, quite often, these changes, on the contrary, trigger a cascade of events leading to epilepsy and long-term disturbances in the functioning of neural networks. Over the past 10 years, significant progress has been achieved in deciphering these changes and their mechanisms, which is covered in our review. However, until now, researchers have not yet reached consensus on which particular modifications in the functioning of synapses provide optimal compensation and are able to prevent epileptogenesis. This knowledge could be the basis for the development of effective methods for epileptogenesis prevention and epilepsy treatment.