Visual experience is one of the factors which influences the formation of nerve connections in the developing brain. A dramatic example of this effect occurs in the development of binocular input to the tectum of the frog, Xenopus laevis. In this species, normal vision is necessary for proper positioning of terminals from the nucleus isthmi (NI), a midbrain structure which projects to the tectum. If eye position is abnormal, then connections from the NI form in the wrong locations. Anterograde labeling of isthmo-tectal axons show that most normal axons travel straight to their proper locations but that axons in abnormal animals often follow very circuitous routes and put our branches at inappropriate sites. In order to understand what leads to these patterns, axons will be labeled in developing animals as well as in adults. In particular we will examine whether axons initially terminate at random and then later restrict their connections to a limited region. Another topographic input to the tectum is the uncrossed isthmo-tectal projection. Lesion studies and electrophysiological recordings will be used to determine whether this input is necessary for formation of an appropriately oriented map from the crossed isthmo-tectal projection. The synaptic interrelationships of retino-tectal axons, isthmo-tectal axons and tectal cells will be studied to determine how information may be conveyed from retinotectal terminals to growing isthmo-tectal terminals. The insights which we gain from studying this relatively simple system in the frog brain will help us to understand comparable phenomena in the more complex brains of mammals. In particular, we know that connections in the developing mammalian brain cortex are affected by abnormal eye position (strabismus), and previous experience indicates that any development principles which we find in frogs will apply to mammals as well.
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