High-frequency network activity, global increase in neuronal activity, and synchrony expansion precede epileptic seizures in vitro.
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) (>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 HFA are 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.
Jiruska
Premysl
P
Neuronal Networks Group, School of Clinical and Experimental Medicine, The University of Birmingham, Birmingham B15 2TT, United Kingdom.
Csicsvari
Jozsef
J
Powell
Andrew D
AD
Fox
John E
JE
Chang
Wei-Chih
WC
Vreugdenhil
Martin
M
Li
Xiaoli
X
Palus
Milan
M
Bujan
Alejandro F
AF
Dearden
Richard W
RW
Jefferys
John G R
JG
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology; D003344:Cortical Synchronization; D004827:Epilepsy / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D009415:Nerve Net / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
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