Connectivity of neural transplants in adult rats: Analysis of afferents and efferents of neocortical transplants in the cerebellar hemisphere

Abstract

Embryonic neocortical tissue, 3.5 mm 3 in volume, obtained from 17-day-old Long-Evans rat embryos, was transplanted into the intact cerebellar hemisphere of normal adult rat hosts. Transplants examined 90–160 days later had grown to a final volume of 27.24 mm 3, which reflected nearly an 8-fold increase in the initial volume of tissue transplanted. The transplants were all lobule during their course of growth and differentiation. They retained a cellular and cytoarchitectural identity characteristic of neocortical tissue. Anterograde degeneration studies and retrograde tracing methods on the light microscopic level revealed that transplants had received afferent connections from the ponto-, olivo- and spinocerebellar projection systems. In addition to these major connections, afferents from other nuclei such as the locus coeruleus and the lateral reticular nucleus were also observed with the HRP method. Efferent outgrowth as studied with degeneration methods revealed projections to the nearby host cerebellum and to the ipsilateral deep cerebellar nuclei. All transplants had developed massive intratransplant connections. Findings on the nature and magnitude of connections were analyzed in terms of different characteristics of the interface between the transplant and the host brain tissue. The surface of cortical transplants was found to consist of 7 distinct components, 5 of which were interface regions. Two types of interface regions, those between the cerebellar medullary and granular layers and transplants, were readily related to the magnitude of extrinsic afferent ingrowth, and hence were effective sprouting surfaces. Using two correlated estimates of the magnitude of afferent ingrowth to cortical transplants, volume of degeneration and surface area of degeneration of transplants resulting from lesions of host brain structures, the pontine system was found to provide more afferents to transplants than the olivary or spinal systems. Generally, extrinsic fibers were located nearer to transplant-host brain interface regions than deep within transplants. A positive correlation existed between the available effective sprouting surface area of transplants (an estimate of interactive host fibers with a suitable trajectory) and the magnitude of innervation of cortical transplants by extrinsic afferents.