Homotopic septal grafts combined with a hydrogel bridge promote functionalrecovery in rats with fimbria-fornix lesions: A unit recording study

Fimbria-fornix lesions abolish the hippocampal electrophysiological activit y time-locked to the theta rhythm and alter some functional characteristics of place cells. The present experiment investigated whether homotopic graf ts of fetal septal cells can alleviate some of these alterations when combi ned with a polymeric hydrogel bridging a fimbria-fornix lesion-cavity. Elev en months after grafting surgery, unit recordings were obtained from hippoc ampal 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 p roducts. Surviving grafts were found in the three grafted rats and several AChE-positive processes could be observed in the polymeric hydrogel, as wel l as in the most dorsal portion of the hippocampal parenchyma. Of 168 recor ded units, 132 were hippocampal interneurons (i.e., fired rapidly everywher e in the maze), and 36 were pyramidal place cells (i.e., fired only when th e 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 di srupted 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 rela tive to extra-maze cues when the radial maze was rotated, while they follow ed the maze rotation in both L and G rats. Because of the low number of rat s used, the present results should be considered with caution. Nevertheless , they indicate graft-induced recovery of some properties of hippocampal fu nction following fimbria-fornix damage, and suggest that homotopic transpla nts of projection neurons may foster some functional recovery when provided with a biomaterial allowing the host or grafted neurons to cross the lesio n cavity.