Understanding the origins of epileptic seizures: This comprehensive review explores the cellular and network mechanisms underlying epileptic seizures in the mammalian forebrain. Focusing on the cerebral cortex and hippocampus, the authors highlight the role of recurrent excitatory connections, intrinsically burst-generating neurons, ephaptic interactions, and synaptic plasticity in generating synchronized activity. In addition, seizures can be generated in response to a loss of balance between excitatory and inhibitory influences and can take the form of either tonic depolarizations or repetitive, rhythmic burst discharges. The paper discusses various forms of epileptiform activity, from the simplest interictal spikes to more complex seizures involving tonic depolarizations or rhythmic burst discharges. It also examines the interplay between the cerebral cortex and thalamus in generating spike waves similar to those observed during human absence seizures. Although epileptic syndromes and their causes are diverse, the cellular mechanisms of seizure generation appear to fall into only two categories: rhythmic or tonic “runaway” excitation or the synchronized and rhythmic interplay between excitatory and inhibitory neurons and membrane conductances. The analysis emphasizes that seizures arise from either runaway excitation or rhythmic interplay between excitatory and inhibitory mechanisms, highlighting the delicate balance that governs normal brain rhythms and cellular mechanisms of seizure generation.
Published in Annual Review of Physiology, this article aligns with the journal's focus on physiological processes in living organisms. By exploring the cellular and network mechanisms of epileptic seizures, this review contributes to the physiological understanding of brain function and its dysregulation in disease. The numerous citations this work has received underscores its significant influence in the neuroscience community.