[Truncated abstract] Formation and consolidation of the retinotectal projection during optic nerve regeneration has been associated with two major interlinked processes. Initially, retinal ganglion cell (RGC) axons are guided by molecular guidance cues, such as the Eph receptor tyrosine kinases and their ligands, the ephrins, to their approximately correct location and form a coarse topographic map in the optic tecum. Such axon guidance occurs in the absence of neural activity and is considered to be activity-independent. The second process involves glutamatergic excitation, whereby correctly located connections are strengthened by correlated neural activity, whilst removing inappropriately located ones thereby sharpening the topography.The second process is considered to be activitydependent. Here, a number of experiments were undertaken to further examine the interrelationships of activity-dependent and independent processes with respect to functional outcomes. Two models of optic nerve regeneration were studied. In goldfish, following optic nerve crush, regeneration is successful. … In goldfish, guidance along the medio-lateral tectal axis may occur through preordering of axons prior to entering the tectum via the appropriate medial and lateral brachium, with EphA/ephrin-A then guiding axons over the rostral-caudal axis establishing gross topography. The increase in involvement of NMDA-mediated transmission during the period of activity-dependent refinement consolidated the role of this receptor in synapse plasticity. However what triggers NMDA-mediated activity to increase is still largely unresolved, although as the factors governing receptor trafficking during development and synaptic plasticity become better understood, these can be applied to the period of plasticity associated with regenerating axons. And finally, as GABAergic inhibition appears to suppress activity-dependent refinement, means of overcoming this inhibition through 4 such methods as visual training or pharmacological intervention may have significance for mammalian regeneration.
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2005|