This review hopes to clearly explain the following viewpoints: (1) Neuronal synchronization underlies brain functioning, and it seems possible that blocking excessive synchronization in an epileptic neural network could reduce or even control seizures. (2) Local field potential coupling is a very common phenomenon during synchronization in networks. Removal of neurons or neuronal networks that are coupled can significantly alter the extracellular field potential. Interventions of coupling mediated by local field potentials could result in desynchronization of epileptic seizures. (3) The synchronized electrical activity generated by neurons is sensitive to changes in the size of the extracellular space, which affects the efficiency of field potential transmission and the threshold of cell excitability. (4) Manipulations of the field potential fluctuations could help block synchronization at seizure onset. Research Highlights (1) Previous studies on epileptic pathogenesis have mainly focused on synaptic transmission and action potential generation. Conventional and novel antiepileptic drugs control epileptic seizures by inhibiting action potentials. Regulatory effects of the extracellular fluid on electric fields and long-range electrical interactions between neurons can explain neuronal hypersynchrony and epileptic activities. (2) This study review evidence of field potential coupling and synchronization of neuronal networks. First, we propose that local field potential coupling plays an important role in synchronization at seizure onset, and suggest that interventions can reduce field potential fluctuations and block early synchronization. Then, we outline the development of a new anti-epileptic treatment based on decoupling of field potentials by electrostimulation.
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