Synapse formation in the olfactory cortex by regenerating optic axons: ultrastructural evidence for polyspecific chemoaffinity.

Abstract

The optic nerve was severed at its entry into the optic chiasma and implanted into the striatal region of the ipsilateral cerebral hemisphere in adult frogs (Rana pipiens). Regenerating retinal ganglion cell axons, observed by the autoradiographic tracing method and by horseradish peroxidase (HRP) fiber filling, grew anteriorly along the olfactory tracts and posteriorly along the ipsilateral lateral forebrain bundle and stria medullaris. Many of the regenerating axons ultimately joined the ipsilateral optic tract. The optic axons formed terminal plexuses in the olfactory cortex, lateral geniculate complex, pretectum, tectum, and basal optical nucleus but not in the amygdala or other cerebral territories not postsynaptic to the olfactory bulb, nor in the cell groups associated with the lateral forebrain bundle or stria medullaris. Optic axon terminals labeled with HRP were observed by electron microscopy in the ipsilateral olfactory cortex and in the normal projection areas of the optic nerve, although they were misplaced to the ipsilateral side. They contained clear, spherical synaptic vesicles and pale mitochondria and made Gray type I, asymmetric contacts on dendrites. The retinal projection to the olfactory cortex was formed early in regeneration and was maintained to some degree for periods up to 39 weeks. It was absent in a specimen surviving 50 weeks. Retinal innervation appeared earlier in the lateral geniculate complex and pretectum than in the tectum. These observations suggest that regenerating retinal ganglion cell axons have an affinity for neurons in the olfactory cortex, as well as for the neurons in the optic pathway to which they are normally postsynaptic. Unless the apparent selectivity of the aberrant projection is regulated by principles other than those that bring about the reinnervation of the normal optic centers, the data further suggest that the nature of the molecular mechanisms conveying synaptic specificity must be broad enough to permit the formation of limited sets of alternative synaptic connections. The ability to innervate selectively targets other than those normally specified is termed, here, polyspecificity. Since polyspecificity refers to the the affinity of retinal ganglion axons, as a class, for target structures considered as unit aggregates, it is conceptually different from the graded affinity of ganglion cells in different regions of the retina for target neurons in different regions of the tectum.(ABSTRACT TRUNCATED AT 400 WORDS)