title: Reorganization of supramammillary-hippocampal pathways in the rat pilocarpine model of temporal lobe epilepsy: evidence for axon terminal sprouting.
abstract: In mesial temporal lobe epilepsy (MTLE), spontaneous seizures likely originate from a multi-structural epileptogenic zone, including several regions of the limbic system connected to the hippocampal formation. In this study, we investigate the structural connectivity between the supramammillary nucleus (SuM) and the dentate gyrus (DG) in the model of MTLE induced by pilocarpine in the rat. This hypothalamic nucleus, which provides major extracortical projections to the hippocampal formation, plays a key role in the regulation of several hippocampus-dependent activities, including theta rhythms, memory function and emotional behavior, such as stress and anxiety, functions that are known to be altered in MTLE. Our findings demonstrate a marked reorganization of DG afferents originating from the SuM in pilocarpine-treated rats. This reorganization, which starts during the latent period, is massive when animals become epileptic and continue to evolve during epilepsy. It is characterized by an aberrant distribution and an increased number of axon terminals from neurons of both lateral and medial regions of the SuM, invading the entire inner molecular layer of the DG. This reorganization, which reflects an axon terminal sprouting from SuM neurons, could contribute to trigger spontaneous seizures within an altered hippocampal intrinsic circuitry.
authors.affiliation: INSERM, UMR 1106, Institut de Neurosciences des Systèmes - INS, 13385, Marseille, France.
authors.forename: Rabia
authors.initials: R
authors.lastname: Soussi
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Boulland
authors.forename: Emilie
authors.initials: E
authors.lastname: Bassot
authors.forename: Hélène
authors.initials: H
authors.lastname: Bras
authors.forename: Patrice
authors.initials: P
authors.lastname: Coulon
authors.forename: Farrukh Abbas
authors.initials: FA
authors.lastname: Chaudhry
authors.forename: Jon
authors.initials: J
authors.lastname: Storm-Mathisen
authors.forename: Lotfi
authors.initials: L
authors.lastname: Ferhat
authors.forename: Monique
authors.initials: M
authors.lastname: Esclapez
mesh_terms: D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000473:pathology*; D006624:Hippocampus / Q000503:physiopathology*; D007034:Hypothalamus, Posterior / Q000503:physiopathology*; D008297:Male; D018721:Muscarinic Agonists; D009434:Neural Pathways / Q000503:physiopathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010862:Pilocarpine / Q000633:toxicity; D017729:Presynaptic Terminals / Q000473:pathology*; D011820:Rabies virus / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
chemical_list: D003911:Dextrans; D018721:Muscarinic Agonists; C493475:Slc17a6 protein, rat; D050599:Vesicular Glutamate Transport Protein 2; C076397:biotinylated dextran amine; D010862:Pilocarpine; D001710:Biotin; D010751:Phosphopyruvate Hydratase