Abstracts

Rationale: The physiologic theta rhythms of the hippocampus are altered in Temporal Lobe Epilepsy (TLE) and in the associated model induced by pilocarpine in the rat (Chauvière et al., J. Neurosci. 2009 Apr 29; 29(17):5402-10). The supramammillary nucleus (SuM), a brain area located in the caudal part of the hypothalamus, is known to play a central role in the regulation of these rhythms (Vertes et Kócsis, Neuroscience 1997 Dec; 81(4):893-926; Kirk, Neurosci. Biobehav. Rev. 1998 Mar; 22(2):291-302). The neurons of the SuM project prominently to the supragranular layer of the dentate gyrus and to the CA2-pyramidal cell layer of the hippocampus (Wyss et al., Anat. Embryol. (Berl). 1979 Jun 5; 156(2):165-76; Haglund et al., J. Comp. Neurol. 1984 Oct 20; 229(2):171-85; Maglóczky et al., Hippocampus 1994 Jun; 4(3):322-34). In our study, we assessed the hypothesis of a reorganization of the supramammillo-hippocampal pathway in the rat pilocarpine model. Methods: This pathway was examined in control and in Pilocarpine-treated rats with chronic limbic seizures by means of: 1) anterograde tracing experiments using a biotinylated dextran amine (BDA) tracer injected under stereotaxic conditions into the SuM; 2) an immunohistochemical labeling for the vesicular glutamate transporter 2 (VGLUT2); 3) double immuno-labelings for BDA and VGLUT2; 4) In situ hybridization experiments for the detection of VGLUT2 mRNA-containing cells. Results: We report: 1) an aberrant density and distribution of VGLUT2-containing terminals in all epileptic pilocarpine-treated rats. A very dense labeling of VGLUT2-containing terminals was present within the entire inner one-third of the molecular layer of the dentate gyrus in epileptic rats, whereas in control animals VGLUT2-containing terminals were restricted to the supragranular layer. 2) Absence of VGLUT2 mRNA expression by the principal neurons of the hippocampal formation including granular cells of the dentate gyrus, in epileptic as in control animals. 3) An aberrant distribution of BDA-labeled axonal fibers and of axon terminals double-labeled for BDA and VGLUT2 within the inner one-third of the molecular layer in all epileptic pilocarpine-treated rats. Conclusions: These data demonstrate a clear reorganization of the SuM-glutamatergic afferences innervating the dentate gyrus in pilocarpine-treated rats with chronic seizures. Whether such reorganization participates to the alteration of the hippocampal theta rhythm frequency, observed in this model of Mesial Temporal Lobe Epilepsy, remains to be demonstrated.