The long term objective and aim of this proposal is to study the development of a neural transplant (Tx), its connectivity and behavioral recovery. It is intended to use Tx procedures to study events and problems of development and age-related developmental plasticity after lesions.
The specific aims are to recreate a model sensory system, with Tx of appropriate neural tissue, and to study the morphological conditions associated with potential re-establishment of function after debilitating brain injury. The olfactory system (OS) of the rat will be used as a model and deafferentation of olfactory cortex (OC) will be accomplished by olfactory bulb (OB) removal and subsequent Tx of fetal OBs. Although the system is well suited for investigations of this type due to its unique organization, it is little studied in Tx research, and thus provides fresh new conditions for investigation of questions of developmental repair, regeneration and potential for behavioral recovery. Whole OBs from embryonic rats labeled in utero will be Tx into the sites vacated by removal of the OB from hosts of different ages. Several features of the maturation of the Tx OB will be studied at various post Tx-times and will be correlated with functional activity and behavioral recovery. Techniques to be used include: conventional light microscopy (LM); electron microscopy (EM); immunocytochemical localization of selected neurotransmitters and nerve growth factor (or its receptor); neuronal transport; autoradiography, degeneration methods; and protocols to assess possible functional activity of the cells involved. Olfactory discrimination testing will be carried out during maturation of the Tx to analyze the behavioral recovery and functional efficacy of the Tx. Special attention will be given to the neurochemical and growth factor related organization or reorganization of the developing Tx. This will be correlated with the development of the connectivity (to and from the Tx) and finally the possible behavioral recovery of the Tx system. Special attention will be placed on the age relationship at the time of Tx, the maturation of the Tx and its connections at these ages, and then related to the functional and behavioral recovery. The results should provide new data on variables directly affecting the potential for developmental plasticity after injury and possible limitations for functional/behavioral recovery.
