Long-lasting modification of intrinsic discharge properties in subicular neurons following status epilepticus.
A single episode of status epilepticus (SE) induces neuropathological changes in the brain that may lead to the development of a permanent epileptic condition. Most studies of this plasticity have focused on the hippocampus, where both synaptic function and intrinsic neuronal excitability have been shown to be persistently modified by SE. However, many other brain structures are activated during SE and may also be involved in the subsequent epileptogenic process. Here we have investigated whether SE, induced in rats with pilocarpine and terminated after 40 min with diazepam, persistently modifies the intrinsic excitability of pyramidal neurons in the subiculum. Subicular slices were prepared from control and SE-experienced rats (2-5 weeks after SE). In the control group, only 4% of the neurons fired bursts in response to intrasomatic, threshold-straddling depolarizing current pulses (low-threshold bursters). The remaining neurons either fired bursts in response to strong (3x threshold) depolarizations (35%; high-threshold bursters) or fired in a completely regular mode (61%; nonbursters). In the SE-experienced group, the fractions of low- and high-threshold bursters markedly increased to 29% and 53%, respectively. This change in firing behaviour was associated with a marked increase in the size of the spike after depolarization, particularly in low-threshold bursters. Experimental suppression of Ca2+ currents selectively blocked low-threshold bursting but did not affect high-threshold bursting, suggesting that a dual Ca2+- dependent and Ca2+- independent mechanism controls bursting in these neurons. The persistent up-regulation of intrinsic bursting in the subiculum, in concert with similar changes in the hippocampus, undoubtedly contributes to epileptogenesis following pilocarpine-induced SE.
Wellmer
Jörg
J
Department of Epileptology, University of Bonn Medical Center, Sigmund-Freud Str. 25, 53105 Bonn, Germany.
Su
Hailing
H
Beck
Heinz
H
Yaari
Yoel
Y
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology; D004833:Epilepsy, Temporal Lobe / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D010862:Pilocarpine / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D000927:Anticonvulsants; D015220:Calcium Channels; D018721:Muscarinic Agonists; D010862:Pilocarpine; D003975:Diazepam