AFFERENT AND EFFERENT CONNECTIVITY OF NEOCORTICAL TRANSPLANTS IN THE CEREBELLAR HEMISPHERE OF THE RAT: A STUDY OF AGE DIFFERENCES IN NEUROPLASTICITY

MONICA MARIE OBLINGER, Purdue University

Abstract

Transplantation of neural tissues in the mammalian brain has provided a useful tool to both the study of neuroembryology and regenerative phenomena in the CNS. In the present research the technique of embryonic transplantation has been used to examine the effect of the host animal age on the nature and magnitude of axonal connections formed by cortical tranplants in the cerebellum. In addition the factors that could account for a differential response were examined. Embryos from Long-Evans female rats on the 17th gestational day provided donor tissue. Embryonic cortex (3.5 mm('3)) was transplanted into the right cerebellar hemisphere of host rats aged 5, 15, 30 or 90 days. Three months later, the survival of transplants, their cytology and characteristics of transplant incorporation into the host brain were examined. The connectivity of fully grown transplants was examined by anterograde and retrograde axonal tracing procedures. Electrolytic lesions of the contralateral pontine nuclei, contralateral olivary nuclei, contralateral cerebellum, ipsilateral ventral thalamus and surgical hemisections of the ipsilateral cervical spinal cord followed by Fink-Heimer staining provided information on afferents to transplants. Injections of HRP into transplants were used to corroborate these findings. Following lesions of pontine, olivary or spinal regions of the host brain, degenerating fibers were traced into cortical transplants in hosts of all ages. Afferents were found to enter cortical transplants through regions of interface between transplant and the cerebellar medullary and granular layers. Following HRP injections into transplants labelled neurons were found mainly in the pons, olive and spinal cord regions, and occasionally in the locus coeruleus, lateral reticular nucleus and vestibular nuclei. The relative magnitude of afferent innervation as well as aspects of transplant integration in terms of surface apposition in animals of different ages was assessed using computer assisted analysis. Transplants placed in younger host animals attained significantly larger total volumes than those from older hosts. The proportion of transplant volume that contained degenerating axons and terminals to the total volume was similar in all host age groups, indicating that larger amounts of transplants contained extrinsic afferents in younger hosts. The amount of transplant surface that contained degenerating host axons following lesions was larger in older host animals. Normalized quantitative measures revealed first, that, although in immature host conditions (5, 15 day) transplants had developed smaller amounts of effective interface with host cerebellum than in older host conditions (30, 90 day), slightly larger volumes of transplants contained extrinsic afferents in younger hosts. Secondly, this was seen to be due to the fact that in immature host conditions afferent axons that had sprouted into transplants grew for longer distances and ramified more extensively than those in older hosts. In all cases, the pontine afferent innervation was larger than olivary or spinal, reflecting the normal topography and characteristics of these systems in the normal brain. Information on efferents of cortical transplants was obtained following electrolytic lesions of transplants and staining for degenerating axons with the Fink-Heimer method. Many intratransplant connections, and efferents to the nearby cerebellum and deep cerebellar nuclei were found in all host groups. Some efferents to the lower brain stem were found in neonate conditions. As such, the efferents were atypical of neocortex and followed a pattern characteristic of the normal cerebellar hemisphere which the transplants had replaced.

Degree

Ph.D.

Subject Area

Anatomy & physiology

COinS