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High-Frequency Network Activity, Global Increase in Neuronal Activity, and Synchrony Expansion Precede Epileptic Seizures In Vitro

Jiruska, Premysl and Csicsvari, Josef and Powell, Andrew D and Fox, John E and Chang, Wei-Chih and Vreugdenhil, Martin and Li, Xiaoli and Palus, Milan and Bujan, Alejandro F and Dearden, Richard W and Jefferys, John G R (2010) High-Frequency Network Activity, Global Increase in Neuronal Activity, and Synchrony Expansion Precede Epileptic Seizures In Vitro. The Journal of Neuroscience, 30 (16). pp. 5690-5701. ISSN 0270-6474

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URL of Published Version: http://www.jneurosci.org/cgi/content/full/30/16/5690

Identification Number/DOI: 10.1523/JNEUROSCI.0535-10.2010

How seizures start is a major question in epilepsy research. Preictal EEG changes occur in both human patients and animal models, but their underlying mechanisms and relationship with seizure initiation remain unknown. Here we demonstrate the existence, in the hippocampal CA1 region, of a preictal state characterized by the progressive and global increase in neuronal activity associated with a widespread buildup of low-amplitude high-frequency activity (HFA) (greater than 100 Hz) and reduction in system complexity. HFA is generated by the firing of neurons, mainly pyramidal cells, at much lower frequencies. Individual cycles of HFAare generated by the near-synchronous (within approximately 5 ms) firing of small numbers of pyramidal cells. The presence of HFA in the low-calcium model implicates nonsynaptic synchronization; the presence of very similar HFA in the high-potassium model shows that it does not depend on an absence of synaptic transmission. Immediately before seizure onset, CA1 is in a state of high sensitivity in which weak depolarizing or synchronizing perturbations can trigger seizures. Transition to seizure is characterized by a rapid expansion and fusion of the neuronal populations responsible for HFA, associated with a progressive slowing of HFA, leading to a single, massive, hypersynchronous cluster generating the high-amplitude low-frequency activity of the seizure.

Type of Work:Article
Date:21 April 2010 (Publication)
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experiment Medicine, School of Computer Science
Subjects:RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
QP Physiology
Institution:University of Birmingham, University of Oxford, Academy of Sciences, Czech Republic
Copyright Holders:The Authors
ID Code:359
Refereed:YES
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