Septotemporal Position in the Hippocampal Formation Determines Epileptic and Neurogenic Activity in Temporal Lobe Epilepsy

• Published in: Cerebral cortex (New York, N.Y. 1991) N.Y. 1991), 2012-01, Vol.22 (1), p.26-36
• Main Authors: Häussler, Ute, Bielefeld, Lena, Froriep, Ulrich P., Wolfart, Jakob, Haas, Carola A.
• Format: Article
• Language: English
• Subjects: 2-Amino-5-phosphonovalerate - pharmacology; 6-Cyano-7-nitroquinoxaline-2,3-dione - pharmacology; Analysis of Variance; Animals; Bromodeoxyuridine - metabolism; Cell Count; Cell Proliferation; Convulsants - pharmacology; Disease Models, Animal; Electric Stimulation; Electroencephalography; Epilepsy, Temporal Lobe - chemically induced; Epilepsy, Temporal Lobe - pathology; Epilepsy, Temporal Lobe - physiopathology; Excitatory Amino Acid Antagonists - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Functional Laterality; Hippocampus - pathology; Hippocampus - physiopathology; Kainic Acid - toxicity; Luminescent Proteins - genetics; Lysine - analogs & derivatives; Lysine - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Motor Activity - genetics; Motor Activity - physiology; Neurogenesis - genetics; Neurogenesis - physiology; Neuropeptides - genetics; Neuropeptides - metabolism; Patch-Clamp Techniques; Picrotoxin - pharmacology
• ISSN: 1047-3211; 1460-2199
• DOI: 10.1093/cercor/bhr054

It is a matter of ongoing debate whether newly generated granule cells contribute to epileptic activity in the hippocampus. To address this question, we investigated neurogenesis and epileptiform activity (EA) along the hippocampal septotemporal axis in the intrahippocampal kainate (KA) mouse model for temporal lobe epilepsy. Multisite intrahippocampal in vivo recordings and immunolabeling for c-Fos showed that the KA-induced status epilepticus (SE) extended along the septotemporal axis of both hippocampi with stronger intensity at ipsilateral temporal and contralateral sites. Accordingly, we found a position-dependent increase in proliferation (incorporation of bromodeoxyuridine) and neurogenesis (immunolabeling for doublecortin): Both were selectively increased in the ipsilateral temporal and entire contralateral subgranular zone, sparing the septal region close to the injection site. The newborn neurons were hyperexcitable and functionally integrated into the hippocampal network as revealed by patch-clamp recordings. Analysis of chronic EA also showed a differential intensity pattern along the hippocampal axis: EA was low in the septal portion with prominent sclerosis and granule cell dispersion but most pronounced in the transition zone where neurogenesis reappeared. In conclusion, SE stimulates neurogenesis in a position-dependent manner and coincidence of neurogenesis and stronger EA distal to the injection site suggests a proepileptogenic effect of increased neurogenesis.