The long-term goal of this research proposal is to determine whether manipulation of the glial cell environment of a lesion cavity similarly enhances or impedes the growth of olfactory and non-olfactory axons in the adult mammalian CNS. One important difference between the primary olfactory system and other regions of the CNS is the glial cell environment through which the olfactory axons must grow. The working hypothesis is that the discrepancy in the growth of olfactory as opposed to non-olfactory axons in the CNS of adult mammals is due to the different glial cell environments through which the axons must grow. The proposed experiments involve manipulation of the glial cell environment of lesion cavities in the primary olfactory pathway and in the corpus callosum, and compares the effect of this manipulation on the growth of olfactory and non-olfactory axons.
The specific aims are: a) to demonstrate in vivo that altering the phenotype of glial cells has a similar effect on the growth of both olfactory and nonolfactory axons; b) to establish in vivo that the glial cell environment of the CNS portion of the primary olfactory pathway promotes the growth of both olfactory and non-olfactory axons; c) to show in vivo that the glial cell environment of a non-olfactory CNS pathway promotes very limited growth of both olfactory and non-olfactory axons; d) to determine whether the basal laminae produced by myelinating glial cells can support the growth of both groups of axons. Selected glial cell populations will be grown on a collagen substratum in vitro in the presence or absence of neurons and in different types of media to influence the cellular phenotype. This collagen substratum is subsequently used to transplant strips of each glial cell culture into preformed lesion cavities in the primary olfactory and callosal pathways. These experiments will identify some of the nonneuronal factors that modulate the growth of olfactory axons and the extent to which this growth is under the same regulatory control as exists for axons in other regions of the CNS.
