Abstract

Transplants of embryonic nervous tissue ameliorate motor deficits induced by motor cortex lesions in adult animals. Restoration of lost brain functions has been recently shown in grafts of homotopic cortical origin, to be associated with a functional integration of the transplant after development of reciprocal host–graft connections. Nevertheless little is known about physiological properties or gene expression profiles of cortical implants with functional restorative capacity but no cortical origin. In this study, we show molecular and electrophysiological evidence supporting the functional development and integration of heterotopic transplants of embryonic amygdalar tissue placed into pre-lesioned motor cortex of adult rats. Grafts were analyzed 3 months post-transplantation. Using reverse transcriptase quantitative polymerase chain reaction, we found that key glutamatergic, GABAergic, and muscarinic receptors transcripts were expressed at different quantitative levels both in grafted and host tissues, but were all continuously present in the graft. Parallel sharp electrode recordings of grafted neurons in brain slices showed a regular firing pattern of transplanted neurons similar to host amygdalar pyramidal neurons. Synaptic connections from the adjacent host cortex on grafted neurons were electrophysiologically investigated and confirmed our molecular results. Taken together, our findings indicate that grafted neurons from a non-cortical, non-motor-related, but ontogenetical similar source, not only received functionally effective contacts from the adjacent motor cortex, but also developed electrophysiological and gene expression patterns comparable to host pyramidal neurons; suggesting an interesting tool for the field of neural repair and donor tissue in adults.

Highlights

  • It is believed that the function of a neural system results from the high balance and level of specificity of its synaptic connections

  • It has been observed that heterotopic transplants of amygdalar embryonic tissue grafted in adult rats following motor cortex lesion induce the same level of behavioral graft-dependent recovery as homotopic grafts (Heredia et al, 2004), suggesting a similar functional integration of the grafted tissue

  • Besides analyzing astrogliosis induced by graft integration, we provide quantification of the relative mRNA levels of glutamatergic, GABAergic, and muscarinic receptors in the graft and host tissues by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), and electrophysiological analysis of transplanted neurons and their synaptic afferents coming from host adjacent tissue

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Summary

Introduction

It is believed that the function of a neural system results from the high balance and level of specificity of its synaptic connections. Embryonic tissue transplanted into the damaged cortex of adult rats has shown successful survival and establishment of reciprocal connections between the host and grafted tissue (Castro et al, 1988; Xu et al, 1991; Plumet et al, 1993; Roger and Ebrahimi-Gaillard, 1994; Frappe et al, 1999; Chen et al, 2002; Gaillard et al, 2007; Gaillard and Domballe, 2008; Santos-Torres et al, 2009) and has lead to behavioral graft-dependent recovery (Labbe et al, 1983; Fernandez-Ruiz et al, 1991; Plumet et al, 1991; Riolobos et al, 2001; Heredia et al, 2004). It has been observed that heterotopic transplants of amygdalar embryonic tissue (a non-cortical and non-motorrelated tissue) grafted in adult rats following motor cortex lesion induce the same level of behavioral graft-dependent recovery as homotopic grafts (Heredia et al, 2004), suggesting a similar functional integration of the grafted tissue

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