The effects of intrahippocampal grafts, training, and postoperative housing on behavioral recovery after septohippocampal damage in the rat

Abstract

This study examined whether the expression of behavioral effects of grafts rich in cholinergic neurons placed into the hippocampus of rats with septohippocampal damage may be modulated by postoperative housing or training conditions. Among 91 Long-Evans female rats, 61 sustained a bilateral aspirative lesion of the fimbria-fornix fibers and all overlying tissue, while 30 were given sham operations. Ten days after surgery, fetal septal suspension grafts were performed in the hippocampus of half the lesioned rats. Two days later, all rats were randomly assigned to one of three housing or training conditions: standard, standard with daily training, and enriched. Two and 5 months later, the rats were tested for learning using a Hebb-Williams maze. At both these delays, performance was clearly impaired in lesioned rats and was found to be ameliorated by grafts only in rats which had received daily training. Cresyl violet staining and acetylcholinesterase histochemistry showed that, irrespective of the housing or training conditions, all grafts had survived and provided the denervated hippocampus with a substantial cholinergic reinnervation. Our results suggest that the beneficial behavioral effects of intrahippocampal suspension grafts of septal cells may depend on the postsurgical training or handling conditions of the graft recipients. This result might be of importance for interpreting some behavioral effects of grafts, since in most studies in which grafts were found to induce beneficial behavioral effects (especially on learning capacity), these effects were generally observed at the end of a rather long testing period. Moreover, the present findings show that this delay, before graft function is expressed, might be linked not only to the time needed by grafts to establish a functional reinnervation in the host brain, but also to the training and/or handling conditions of the graft recipient.