Affiliations: Laboratoire de Neurosciences Comportementales et
Cognitives, CNRS, Université Louis Pasteur, Strasbourg, France | Centre de Recherche en Neurosciences Cognitives, CNRS,
Marseille, France | Organogel Canada Ltée, Québec,
Canada
Abstract: Fimbria-fornix lesions abolish the hippocampal electrophysiological
activity time-locked to the theta rhythm and alter some functional
characteristics of place cells. The present experiment investigated whether
homotopic grafts of fetal septal cells can alleviate some of these alter-ations
when combined with a polymeric hydrogel bridging a fimbria-fornix
lesion-cavity. Eleven months after grafting surgery, unit recordings were
obtained from hippocampal neurons of seven rats [two sham-operated (S), two
lesion-only (L) and three grafted (G)] while they explored a radial maze. The
lesions induced dramatic loss of hippocampal
acetylcholinesterase(AChE)-positive reaction products. Surviving grafts were
found in the three grafted rats and several AChE-positive processes could be
observed in the polymeric hydrogel, as well as in the most dorsal portion of
the hippocampal parenchyma. Of 168 recorded units, 132 were hippocampal
interneurons (i.e., fired rapidly everywhere in the maze), and 36 were
pyramidal place cells (i.e., fired only when the rat was in a specific location
in the maze, the place field). The overall firing characteristics of either
cell type were similar in S, L and G rats. However, while none of the
interneurons recorded from L rats was found to fire rhythmically, a
significant proportion of interneurons recorded from S and G rats had an
activity pattern time-locked to the theta rhythm [S: 16/19 (84 %); G : 22/70
(31 %)]. In addition, the increase in firing activity observed in interneurons
recorded from S rats when they were moving was disrupted in cells from L rats,
but partially restored in cells from G rats. Concerning place cells, most (93
%) place fields in S rats were stable relative to extra-maze cues when the
radial maze was rotated, while they followed the maze rotation in both L and G
rats. Because of the low number of rats used, the present results should be
considered with caution. Nevertheless, they indicate graft-induced recovery of
some properties of hippocampal function following fimbria-fornix damage, and
suggest that homotopic transplants of projection neurons may foster some
func-tional recovery when provided with a biomaterial allowing the host or
grafted neurons to cross the lesion cavity.
