Uncovering cytoplasmic domains of NMDA receptors important for basal and activity-dependent trafficking to synapses

Glutamate receptors are important for excitatory transmission between neurons and for basic neural function, and the NMDA-type glutamate receptor is widely expressed in the brain. Studies investigating the role of NMDA-type glutamate receptors have implicated their function in schizophrenia, pain, ischemia, addiction, synaptic plasticity and learning and memory. The majority of NMDA receptors cluster at synapses: interactions of certain regions of the receptor with proteins in the cell govern their transport and localization to the synapse. The number of NMDA receptors at synapses, and the composition of the subunits that make up the receptors, are important elements of the overall function of the nervous system. MSFHR funded Jacqueline Rose for her PhD work, where she used the microscopic worm C. elegans as a model to analyze how mutations in Presenilin genes affect learning and memory. Now, Jackie is researching the molecular mechanisms underlying the transport of NMDA-type glutamate receptors to synapses, and determining how this affects plasticity, thought to underlie memory and learning, at the cellular level. By developing specific mutations that will prevent certain proteins from interacting with particular NMDA-type glutamate receptor subunits, she hopes to shed further light on the receptor regions necessary for glutamate receptors to move to synapses during activity-dependent plasticity.