Newly formed excitatory pathways provide a substrate for hyperexcitability in experimental temporal lobe epilepsy.
Temporal lobe epilepsy (TLE) in humans and animals is associated with axonal sprouting of glutamatergic neurons and neosynaptogenesis in the hippocampal formation. We examined whether this plasticity of excitatory pathways contributes to an increased level of glutamatergic excitation in the CA1 region of rats experiencing chronic spontaneous limbic seizures following kainic acid or pilocarpine treatment. In chronic cases, we report an extensive axonal sprouting of CA1 pyramidal neurons, with many axonal branches entering the pyramidal cell layer and stratum radiatum, regions that are not innervated by axonal collaterals of CA1 pyramidal neurons in control animals. Concurrently with this anatomical reorganization, a large increase of the spontaneous glutamatergic drive is observed in the dendrites and somata of CA1 pyramidal cells. Furthermore, electrical activation of the reorganized CA1 associational pathway evokes epileptiform bursts in CA1 pyramidal cells. These findings suggest that reactive plasticity could contribute to the hyperexcitability of CA1 pyramidal neurons and to the propagation of seizures in these two models of TLE.
Esclapez
M
M
INSERM Unité 29, Paris, France.
Hirsch
J C
JC
Ben-Ari
Y
Y
Bernard
C
C
D000818:Animals; D001369:Axons / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D004594:Electrophysiology; D004833:Epilepsy, Temporal Lobe / Q000473:pathology / Q000503:physiopathology*; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted; D008239:Lysine / Q000031:analogs & derivatives; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013569:Synapses / Q000502:physiology
D018698:Glutamic Acid; C013411:biocytin; D008239:Lysine