Event Details:
Special Seminar
Regulation of Neurotransmitter Receptors During Synaptic Plasticity in Health and Disease
Speaker
Richard L. Huganir
Bloomberg Distinguished Professor of Neuroscience and Physiological and Brain Sciences
Director, Department of Neuroscience
Johns Hopkins University School of Medicine
Host: Kang Shen
Abstract
Neurotransmitter receptors mediate signal transduction at synaptic connections between neurons in the brain. My laboratory has been elucidating the molecular mechanisms underlying the regulation of glutamate receptors, the major excitatory neurotransmitters receptors in the central nervous system. We have focused on AMPA-type glutamate receptors and have found that they are extensively posttranslationally modified by phosphorylation, palmitoylation and ubiquination. We have shown that these posttranslational modifications of the receptor regulates its ion channel properties and membrane trafficking and are critical for several forms of synaptic plasticity and for learning and memory. We have also identified a variety of AMPA receptor interacting proteins, including GRIP1/2, PICK1, GRASP1, SNX27, KIBRA, and SynGAP, that interact with AMPA receptors and are necessary for their proper subcellular trafficking and synaptic targeting. This AMPA receptor complex is important for several forms of synaptic plasticity and learning and memory. These studies indicate that the modulation of receptor function is a major mechanism for the regulation of synaptic transmission and is a critical determinant of animal behavior. Recent evidence has indicated that AMPA receptor function may be disrupted in several neurological and psychiatric disorders. Specifically, mutations in the AMPA receptor complex have been found to be associated with cognitive disorders including intellectual disability, autism, and schizophrenia. We have recently been attempting to develop potential therapies for these devastating disorders based on these findings.