Richard Huganir

Summary

Professor and Director, Department of Neuroscience at Johns Hopkins University
Co-Director, Brain Science Institute; and HHMI investigator
President, Society for Neuroscience (2017-2018)
Member, Multi-Council Working Group (NIMH council)

Huganir's lab is credited for examining the molecular mechanisms underlying the regulation of neurotransmitter receptor function with a focus on glutamate receptors.Their studies have suggested that regulation of receptor function may be a major mechanism for the regulation of synaptic plasticity in the nervous system in health and disease.

 

Information

Department Webpage: neuroscience.jhu.edu/resources/directory/faculty/richard-l.-huganir/
Lab Page: neuroscience.bs.jhmi.edu/huganir/

Email: rhuganir@jhmi.edu
Phone:  410-955-4050
Address: The Solomon H. Snyder Department of Neuroscience
Johns Hopkins University School of Medicine
725 North Wolfe Street
Baltimore, MD 21205
Room: Hunterian 1009A

Research

Regulation of Neurotransmitter Receptors and Brain Function in Health and Disease

Neurotransmitter receptors mediate signal transduction at the postsynaptic membrane of synaptic connections between neurons in the nervous system. We have been studying the molecular mechanisms in the regulation of neurotransmitter receptor function. Recently we have focused on glutamate receptors, the major excitatory receptors in the brain. Glutamate receptors can be divided into two major classes: AMPA and NMDA receptors. AMPA receptors mediate rapid excitatory synaptic transmission while NMDA receptors play important roles in neuronal plasticity and development. Studies in our laboratory have found that both AMPA and NMDA receptors are multiply phosphorylated by a variety of protein kinases. Phosphorylation regulates several functional properties of these receptors including conductance and membrane targeting. Recent studies in our lab have demonstrated that the phosphorylation of AMPA receptors is regulated during cellular models of learning and memory such as long-term potentiation (LTP) and long-term depression (LTD). Moreover, phosphorylation of the AMPA receptor GluR1 subunit is required for the expression of these forms of plasticity and for the retention of spatial memory and also regulates emotional memory formation and erasure.

We have also been examining the mechanisms of the subcellular targeting and clustering of glutamate receptors at synapses. We have recently identified a variety of proteins that directly or indirectly interact with AMPA and NMDA receptors. We have found a novel family of proteins that we call GRIPs (Glutamate Receptor Interacting Proteins) that directly bind to the C-termini of the GluR2/3 subunits of AMPA receptors. GRIPs contain seven PDZ domains, protein-protein interaction motifs, which crosslink AMPA receptors to each other or link them to other proteins. In addition, we have found that the C-termini of GluR2 also interacts with the PDZ domain of PICK1, a protein kinase C-binding protein that is found at excitatory synapses. The GluR2 subunit also interacts with the NSF protein, a protein involved in the regulation of membrane fusion events. These AMPA receptor interacting proteins are critical in the proper membrane trafficking and synaptic targeting of these receptors. We have shown that the binding of PICK1 and GRIP is required for a specific form of LTD in the cerebellum that is a cellular model for motor learning. Moreover, we have found that this receptor complex is critical for hippocampal LTP and LTD and spatial learning.

In addition to these studies on AMPA receptors, we have been characterizing a separate NMDA receptor associated protein complex that is important in synaptic targeting and downstream signaling of NMDA receptors. We have identified an excitatory synapse specific rasGAP, which we call synGAP that regulates synaptic Ras signaling and has profound effects on synaptic plasticity.

Importantly, recent evidence has implicated glutamate receptor associated complexes in several neurological and psychiatric disorders including Alzheimer’s disease, schizophrenia, autism, mental retardation as well as in chronic pain and drug addiction.

In summary, we have examined the molecular mechanisms underlying the regulation of neurotransmitter receptor function. Our studies have suggested that regulation of receptor function may be a major mechanism for the regulation of synaptic plasticity in the nervous system in health and disease and may be an important determinant of animal behavior.

Biography

Dr. Huganir is a member of the National Academy of Sciences and the Institute of Medicine. He is a former chair of the NINDS board of scientific counselors. He is currently the Associate Editor of “Neuron”. His laboratory is credited for examining the molecular mechanisms underlying the regulation of neurotransmitter receptor function with a focus on glutamate receptors. Their studies have suggested that regulation of receptor function may be a major mechanism for the regulation of synaptic plasticity in the nervous system in health and disease and may be an important determinant of animal behavior.

Education

1971-1975 Vassar College, A.B. Biochemistry

1977-1982 Cornell University, Ph.D.

Program in Biochemistry, Molecular and Cell Biology (Thesis Advisor – Dr. Efraim Racker)

Positions Held

2006 – Present
Professor and Director, Department of Neuroscience; Professor Department of Biological Chemistry and Pharmacology and Molecular Sciences; The Johns Hopkins University School of Medicine; Investigator, Howard Hughes Medical Institute

7/93 – 2/2006
Professor, Department of Neuroscience and Department of Biological Chemistry; The Johns Hopkins University School of Medicine; Investigator, Howard Hughes Medical Institute

1/88 – 6/93
Associate Professor, Department of Neuroscience and Department of Biological Chemistry; The Johns Hopkins University School of Medicine; Associate Investigator, Howard Hughes Medical Institut

7/84 – 12/87
Assistant Professor, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University

7/83 – 7/84
Postdoctoral Fellow, Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University (Advisor – Dr. Paul Greengard)

2/82-6/83
Postdoctoral Fellow, Department of Pharmacology, Yale University School of Medicine (Advisor – Dr. Paul Greengard)

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