Spatiotemporal dynamics of high-K+-induced epileptiform discharges in hippocampal slice and the effects of valproate.
The epileptic seizure is a dynamic process involving a rapid transition from normal activity to a state of hypersynchronous neuronal discharges. Here we investigated the network properties of epileptiform discharges in hippocampal slices in the presence of high K(+) concentration (8.5 mmol/L) in the bath, and the effects of the anti-epileptic drug valproate (VPA) on epileptiform discharges, using a microelectrode array. We demonstrated that epileptiform discharges were predominantly initiated from the stratum pyramidale layer of CA3a-b and propagated bi-directionally to CA1 and CA3c. Disconnection of CA3 from CA1 abolished the discharges in CA1 without disrupting the initiation of discharges in CA3. Further pharmacological experiments showed that VPA at a clinically relevant concentration (100 μmol/L) suppressed the propagation speed but not the rate or duration of high-K(+)-induced discharges. Our findings suggest that pacemakers exist in the CA3a-b region for the generation of epileptiform discharges in the hippocampus. VPA reduces the conduction of such discharges in the network by reducing the propagation speed.
Department of Neurology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Jian-Sheng
JS
Liu
Jing-Bo
JB
Li
Xin-Wei
XW
Gong
Hai-Qing
HQ
Gong
Pu-Ming
PM
Zhang
Pei-Ji
PJ
Liang
Qin-Chi
QC
Lu
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001931:Brain Mapping; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium; D017966:Pyramidal Cells / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014635:Valproic Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D014635:Valproic Acid; D011188:Potassium