Studies on the ability of regenerating nerves to relocate their former target tissues and information on the errors made during the regrowth are valuable for the insights they may provide toward a general understanding of the normal and abnormal development of the nervous system and the clinical management of neurological trauma. Optic nerve regeneration proceeds without error in the frog, when the nerve is transected by pinching it gently behind the eye. If the principal target (the midbrain optic tectum) is removed, the regenerating optic nerve forms an anatomically demonstrable synaptic connection with the principal tectorecipient nucleus of the thalamus. This nucleus normally receives its input from the tectum, but is never normally targeted by the retina. If the optic nerve is cut at the optic chiasma and deflected anteriorly into the cerebral hemisphere, the regenerating axons form a synaptic connection in the olfactory cortex. We will study the specificity, stability, and functional status of the aberrant optic projection in the cerebral hemisphere. Our approach to the specificity of the aberrant projection will be to determine whether the optic nerve would target any other cerebral territories if opportunities for greater latitude were increased. We will do this by deleting the normal afferent supply to two territories, the amygdala and the ventral striatum, over which the aberrant optic axons grow when introduced into the cerebral hemisphere by our standard surgical procedure. The olfactory cortex itself will be removed in some specimens to force the choice. This will test the proposition that the developmental specificity of nervous connections is an artifice of a regular program of availability of synaptic space. In other experiments, we will insert the optic nerve at different locations in the cerebral hemisphere to determine whether targets other than the olfactory cortex might be selected if the regenerating fibers approach them by other routes. The stability of the aberrant retino-olfactory projection will be examined in long-term experiments. We will also determine whether reinnervation of the tectum by regenerating axons that escape posteriorly from the nerve implant reduces the stability of the aberrant projection. Since the stability of the aberrant projection may be connected to its functional status, we will attempt to record optically evoked postsynaptic activity in the olfactory cortex.
