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Rita J. Balice-Gordon, PhD
Mechanisms of Autoimmune Synaptopathies
Professor, Department of Neuroscience, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
2 Riverside Circle, Roanoke, VA 24016
Synaptic plasticity is thought to underlie mechanisms of memory, learning, and cognition. Central to these neurological functions is the proper synaptic localization and trafficking of neurotransmitter receptors, including excitatory glutamate NMDARs and AMPARs. The roles of these receptors at the synaptic and cellular level have been established through animal models in which the receptors have been genetically or pharmacologically altered. In humans, the role of these receptors in memory, learning, and cognition comes from more indirect approaches such as pharmacological drug trials—including NMDAR antagonists in schizophrenia—and analysis of brain tissue from patients with disorders such as Alzheimer’s disease and schizophrenia in which multiple genetic or molecular pathways are affected.
Dr. Balice-Gordon’s talk will focus on two recently discovered human autoimmune disorders of memory, learning, cognition, and psychosis in which the patient’s antibodies directly affect the function of NMDARs and AMPARs. These disorders are naturally occurring models of human memory dysfunction that are relatively frequent, cause severe memory loss, can be lethal but are potentially treatable, and often affect children. In addition, patients’ antibodies bind preferentially to the hippocampus, cerebellum, and striatum rather than generally or equally to all brain regions. Dr. Balice-Gordon will discuss her recent published work and unpublished results that establish the cellular and synaptic mechanisms underlying these novel and life-threatening anti-glutamate receptor encephalopathies as well as mechanisms of recovery, provide insights into cellular and circuit dysfunction caused by patients’ antibodies, and begin to connect synaptic and circuit dysfunction with the behavioral abnormalities that are hallmarks of these disorders.