Microcircuits and their interactions in epilepsy: is the focus out of focus?

• Published in: Nature neuroscience Vol. 18; no. 3; pp. 351 - 359
• Main Authors: Paz, Jeanne T, Huguenard, John R
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2015; Nature Publishing Group
• Subjects: 13; 13/51; 14; 14/35; 38; 631/378/1689/178; 631/378/3920; 692/308/1426; 82; 9/26; 9/30; 9/74; Animal Genetics and Genomics; Animals; Anticonvulsants; Behavioral Sciences; Biological Techniques; Biomedicine; Brain - pathology; Brain - physiopathology; Brain research; Convulsions & seizures; Drug therapy; Epilepsy; Epilepsy - pathology; Health aspects; Humans; Nerve Net - physiopathology; Neural networks; Neurobiology; Neurosciences; review-article; United States; United States > US; California
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.3950

In this Review, Jeanne Paz and John Huguenard examine how recent work has informed us on the function of brain microcircuitry and how different circuit types may contribute to seizure generation and/or propagation. The authors also propose the idea that these microcircuits may regulate the spread of seizures and represent new targets for therapeutic intervention. Epileptic seizures represent dysfunctional neural networks dominated by excessive and/or hypersynchronous activity. Recent progress in the field has outlined two concepts regarding mechanisms of seizure generation, or ictogenesis. First, all seizures, even those associated with what have historically been thought of as 'primary generalized' epilepsies, appear to originate in local microcircuits and then propagate from that initial ictogenic zone. Second, seizures propagate through cerebral networks and engage microcircuits in distal nodes, a process that can be weakened or even interrupted by suppressing activity in such nodes. We describe various microcircuit motifs, with a special emphasis on one that has been broadly implicated in several epilepsies: feed-forward inhibition. Furthermore, we discuss how, in the dynamic network in which seizures propagate, focusing on circuit 'choke points' remote from the initiation site might be as important as that of the initial dysfunction, the seizure 'focus'.