Acetylcholine release from intrahippocampal septal grafts is under control of the host brain

The activity of intrahippocampal transplants of cholinergic neurons was monitored by microdialysis in awake, freely moving rats. Fetal septal-diagonal band tissue was implanted into rats with a complete transection of the fimbria-fornix cholinergic pathway either as a cell suspension injected into the hippocampus or as a solid graft implanted in the lesion cavity. The grafts restored baseline acetylcholine release in the graft-reinnervated hippocampus to normal or supranormal levels. The graft-derived acetylcholine release was dependent on intact axonal impulse flow, and it was markedly increased during behavioral activation by sensory stimulation or by electrical stimulation of the lateral habenula. The results demonstrate that the septal grafts, despite their ectopic location, can become functionally integrated with the host brain and that the activity of the transplanted cholinergic neurons can be modulated from the host brain during ongoing behavior. Anatomical observations, using immunohistochemistry and retrograde tracing, indicate that direct or indirect brainstem afferents to the graft could mediate this functional integration. Host afferent control of the graft may thus play a role in the recovery of lesion-induced functional deficits seen with these types of transplants.