Function recovery following neural transplantation of embryonic septal nuclei in adult rats with septohippocampal lesions

doi:doi:10.1038/300260a0

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Nature 300, 260 - 262 (18 November 1982); doi:10.1038/300260a0

Function recovery following neural transplantation of embryonic septal nuclei in adult rats with septohippocampal lesions

Walter C. Low^*§, Peter R. Lewis^*, S. Terri Bunch^*, Stephen B. Dunnett^†, Stephen R. Thomas^†, Susan D. Iversen^†, Anders Björklund^‡ & Ulf Stenevi^‡

^*Physiological Laboratory, University of Cambridge, Cambridge CB2 3EG, UK
^§Present address: Department of Physiology and Biophysics, University of Vermont, Burlington, Vermont 05405, USA.
^†Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, UK
^‡Department of Histology, University of Lund, S-223 62 Lund, Sweden

The remarkable capacity of transplanted embryonic neurones to innervate the hippocampal formation of mature recipients has been well documented, with the pattern of innervation being shown to be anatomically specific and to resemble normal connectivity¹⁻³. Although transplants are known to have functional consequences in other systems⁴⁻⁹, information has yet to be obtained regarding the functional nature of embryonic septal transplants and the behavioural consequences of transplant innervation of the host hippocampal formation. We provide here evidence that a reinnervation of the hippocampal formation from cholinergic-rich septal transplants is functional in terms of the physiology of neural connectivity and that the newly formed connections can interact with an intrinsic afferent system, the perforant path. Moreover, we demonstrate that the reinnervation can aid in the partial recovery of the performance of a radial maze task that is thought to depend on the integrity of septohippocampal connections¹⁰. The behavioural performance of animals with transplants improved significantly compared with those without transplants when both groups were systemically injected with the acetylcholinesterase (AChE) inhibitor, physostigmine. These results suggest that neural transplants from embryonic tissue that reinnervate the hippocampal formation can form functional synaptic connections that can lead to the partial restoration of maze performance.