Short-term frequency-dependent plasticity at recurrent mossy fiber synapses of the epileptic brain.
The recurrent mossy fiber pathway of the dentate gyrus expands dramatically in human temporal lobe epilepsy and in animal models of this disorder, creating monosynaptic connections among granule cells. This novel granule cell network can support reverberating excitation but is difficult to activate with low-frequency stimulation. This study used hippocampal slices from pilocarpine-treated rats to explore the dependence of synaptic transmission in this pathway on stimulus frequency. Minimal electrically evoked EPSCs exhibited a high failure rate ( approximately 60%). Stimulus trains delivered at a frequency of <1 Hz depressed synaptic transmission, as evidenced by an increase in response failures. Conversely, stimulus trains delivered at higher frequencies reduced the percentage of response failures and increased the amplitude of compound EPSCs, including pharmacologically isolated NMDA receptor-mediated EPSCs. Short-term frequency-dependent facilitation was of modest size compared with mossy fiber synapses on other neuronal types. Facilitation depended on the activation of kainate receptors by released glutamate and was inhibited by feedback activation of type II metabotropic glutamate receptors. These results suggest that the recurrent mossy fiber pathway may be functionally silent during baseline asynchronous granule cell activity in vivo attributable, in part, to progressive transmission failure. The pathway may synchronize granule cell firing and may promote seizure propagation most effectively during the brief periods of high-frequency granule cell firing that occur during normal behavior, during the periods of hypersynchronous fast activity characteristic of epileptic brain and, most importantly, during the period of increasing granule cell activity that precedes a spontaneous seizure.
Feng
Li
L
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Molnár
Peter
P
Nadler
J Victor
JV
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010862:Pilocarpine; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D010862:Pilocarpine