Glutamate is the most abundant excitatory neurotransmitter in the brain, and glutamatergic synapses play a critical role in learning, memory, and developmental plasticity of the central nervous system It is critical to understand how glutamatergic synapses are formed and regulated in the CNS in order to develop novel applications for the diagnosis, treatment, and prevention of diseases due to neurodegeneration, spinal cord injury, stroke, drug addiction, schizophrenia, and mood disorders. Several fundamental questions remain unanswered. How are glutamate receptors and signaling molecules localized specifically to glutamatergic synapses? How are these neuron-neuron synapses made and modified during development? To address these questions, we have developed C. elegans as a model system for studying glutamate signaling in vivo with an emphasis on how glutamatergic synapses are formed and modified during development. This has proved to be a powerful genetic system for studying synapse formation, and we have used it to make two novel and interesting observations. First, we have shown that the PDZ-domain protein LIN-10 is a shared component of the polarized protein-sorting pathways in epithelia and neurons, and provided direct evidence that PDZ proteins are required for the localization of neurotransmitter receptors to central synapses in vivo. Second, we have shown that CaMKII facilitates the insertions of receptors into synapses, which suggests a molecular mechanism for how CaMKII signaling can regulate synapses and synaptic plasticity. Our current research focuses on understanding how LIN-10 and CaMKII function to localize glutamate receptors to synapses between neurons, as well as identifying new proteins responsible for localizing glutamate receptors and organizing synapses. Interestingly, we have found that the functions of LIN-10 and CaMKII are both conserved across phylogeny. Thus, we expect our future experiments with this system to reveal universal principles about the formation and function of the central nervous system, and perhaps suggest new strategies for the treatment of human neurological disorders.