Reformation of the severed septohippocampal cholinergic pathway in the adult rat by transplanted septal neurons

Summary

Transplants containing developing cholinergic neurons were obtained from the septum-diagonal band area of rat fetuses and were implanted into a lesion of the septohippocampal cholinergic pathway or into a cavity of the occipital cortex in adult recipient rats. The growth of new cholinergic fibres from the implant into the hippocampal formation was followed with choline acetyltransferase (ChAT) determinations and acetylcholine esterase (AChE) histochemistry. A fimbrial lesion alone, transecting the septohippocampal pathway, caused an almost complete cholinergic denervation of the hippocampal formation that persisted throughout the five month experimental period. A septal transplant implanted into the cavity of the fimbrial lesion restored a new AChE-positive innervation pattern in the hippocampus and the dentate gyrus that closely mimicked the original innervation removed by the lesion. In parallel, there was a progressive recovery in the ChAT levels, starting in the septal end, and progressing in a temporal direction. A new cholinergic fibre supply could be established in the hippocampal formation also along an abnormal route, i.e. from the transplants implanted into a cavity in the occipital cortex (involving also the dorsal part of the entorhinal cortex). Provided the hippocampus previously had been denervated of its normal cholinergic innervation, a partly normal AChE-positive terminal pattern was thus re-established also from this abnormal position. If, on the other hand, the cholinergic afferents were left intact, the ingrowing fibres were restricted mainly to the outer portion of the dentate molecular layer, i.e. the terminal zone of the lesioned entorhinal perforant path fibres. This suggests that the growth of the sprouting AChE-positive fibres into the normal cholinergic terminal fields was blocked by the presence of an intact cholinergic innervation. It is concluded that regrowing cholinergic axons can be guided over large distances within the hippocampal formation, and that their patterning within the terminal fields is very precisely regulated by mechanisms released by deafferentation.