| Early in development the visual circuitry in the brain is highly plastic. Factors that contribute to this plasticity and its expression are synaptic activity and the proteins expressed in the cell. As the system matures this plasticity is expressed and the system changes such that it becomes better at resolving finer details of the environment. Synaptic input from the retina participate in the initiation, progression, and once established the maintenance of visual function. Thus synaptic drive is key to the normal development of vision. However, the exact relationship between synaptic activity with the nature and distribution of proteins is not well established. It is not yet fully clear the extent to which synaptic activity directs the use of proteins in remodeling, modulates the levels of proteins in the cell, and how these changes regulate plasticity in the developing brain.;We propose that synaptic changes and experience-dependent changes in proteins expressed in the cell interact to regulate the functional development of vision. To test this we combined electrophysiology, imaging, and molecular biology to examine the effects of activity on the structure of dendritic arbors, and the properties of glutamatergic synapses, in the retinotectal projection system of the developing Xenopus tadpole. We observed that synaptic activity regulates the activity of the transcription factor Nuclear Factor of Activated T cells (NFAT). Furthermore, we found that distinct NFAT interactions lead to dissociable changes in a-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAr) mediated synaptic strength, and dendritic remodeling. We also show that visual stimulation, sufficient to regulate NFAT activity, leads to increased expression of pro Brain Derived Neurotrophic Factor (proBDNF) in the tectum and that up-regulation of this protein leads to a facilitation of bi-directional plasticity. Finally we show that the facilitation of bi-directional plasticity leads to an improvement in visual acuity. |
