Sensory experience is required for the development of the visual system, however the direct effects of visual experience on the development of the neural circuits in visual centers have been difficult to determine. Development of neural circuits requires that neurons extend axons and dendrites into regions of the brain where they then form and maintain synaptic connections. In order to understand mechanisms controlling circuit development, it is essential to determine the mechanisms that control both the structural development of neurons and the formation of synaptic connections. The primary goal of the experiments in this proposal is to determine the activity-dependent mechanisms that govern the formation of visual system circuits. We address this question by studying the mechanisms that control the development of synaptic connections and neuronal structure in the retinotectal system of Xenopus, using imaging, electrophysiology and molecular biology methods. During the last funding period, we found that a relatively brief period of visual stimulation leads to a significant increase in growth of dendritic arbors of neurons in the optic tectum and that the increased growth of the optic tectal neurons requires glutamatergic synaptic transmission. We now have the unique opportunity to determine direct consequences of sensory experience on the structural and functional development of the visual system. We will express fluorescent proteins in presynaptic retinal axons and postsynaptic optic tectal neurons which allow us to visualize the development of neuronal structures and synapse formation in the intact brain. We propose to determine how visual stimulation and activation of postsynaptic glutamate receptors regulates growth of presynaptic retinal axons, tectal cell dendrites and formation of synaptic connections from the eye into the brain. In addition to addressing fundamental questions regarding mechanisms of synaptogenesis and stabilization, we will determine the effects of visual stimulation, synaptic transmission and glutamate receptor function on visual system development.
Showing the most recent 10 out of 39 publications
