Effects of focal injection of kainic acid into the mouse hippocampus in vitro and ex vivo.
Intra-hippocampal kainate injection induces an epileptiform activity termed status epilepticus. We examined the emergence of this activity with extracellular and intracellular records of responses (1) to focal kainate (KA) application in slices of mouse hippocampus and (2) of slices from mice injected with KA. The effects varied with distance from the injection site of KA. At distances less than approximately 800 microm, KA injection induced a strong increase in extracellular firing which ceased after 2-4 min. Pyramidal cells in this zone fired and depolarized to a potential at which action potentials were no longer evoked. No further activity was detected near the injection site for 3-5 h. In longitudinal slices of the CA3 region, firing induced by KA injection spread at a velocity close to 1 x 10(-)(4) mm ms(-)(1). The velocity increased to approximately 1 x 10(-)(1) mm ms(-)(1) when synaptic inhibition was blocked, suggesting that inhibitory processes normally restrict the spread of firing. At distances of 1.5-2.5 mm, KA injection induced a short-term increase in firing which was maintained, and often increased and rhythmic at gamma frequencies at 2-5 h after injection. We also examined slices prepared from animals injected with KA, at a delay of 2-5 h corresponding to the expression of status epilepticus. Near the injection site, Gallyas silver staining revealed cellular degeneration, and no activity was recorded. Interictal-like activity was generated by ipsilateral slices distant from KA injection. Contralateral slices also generated an interictal-like activity, but no cell death was detected. Hippocampal oscillations generated at distant sites may be associated with status epilepticus.
Le Duigou
Caroline
C
INSERM U739, CHU Pitié-Salpêtrière, 105 boulevard de l'Hôpital, 75013 Paris, France.
Wittner
Lucia
L
Danglot
Lydia
L
Miles
Richard
R
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002470:Cell Survival; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D066298:In Vitro Techniques; D007267:Injections; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology
D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid