Center for Neuroscience
Department of Neurology
I am interested in how NMDA receptors control bidirectional synaptic plasticity.
Regulation of synaptic NMDA receptors
Research in Dr. Gray’s laboratory focuses on understanding the molecular and cellular mechanisms involved in synapse development and plasticity throughout the brain. In particular, Dr. Gray’s laboratory studies the regulation of the NMDA-type glutamate receptors that play crucial roles in synapse development and synaptic plasticity. In addition, NMDA receptors have been implicated in a broad range of neuropsychiatric disorders, including schizophrenia, autism, addiction, Alzheimer’s disease, Huntington’s disease and ischemia. By combining innovative genetic approaches with electrophysiology and imaging to gain a detailed understanding of the molecular mechanisms involved in the regulation of NMDA receptors and synapses, Dr. Gray’s laboratory is striving to open new frontiers for the development of disease-modifying therapeutic approaches for complex neuropsychiatric disorders.
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
- Pharmacology and Toxicology Graduate Group
Specialties / Focus
- Cell Biology
- Developmental Biology
- Molecular Physiology
- Signal Transduction
Honors and Awards
- NIMH Mentored Clinical Scientist Research Career Development Award
- NARSAD 2009 Young Investigator Award
- American College of Neuropsychopharmacology Travel Award
- Society of Biological Psychiatry Travel Fellowship Award
- NIMH Outstanding Resident Award
- Phi Beta Kappa Honor Society
- NARSAD 2015 Young Investigator Award
- 1997 B.S. Biochemistry Case Western Reserve University
- 2003 Ph.D. Biochemistry Case Western Reserve University
- 2005 M.D. Medicine Case Western Reserve University School of Medicine
- 2009 Residency Psychiatry University of California, San Francisco
Crestani AP, Krueger JN, Barragan EV, Nakazawa Y, Nemes SE, Quillfeldt JA, Gray JA, and Wiltgen BJ (2019). Metaplasticity contributes to memory formation in the hippocampus. Neuropsychopharmacology, 44(2): 408-412.
Yang XY, Stanley RE, Ross AP, Robitaille AM, Gray JA, and Cheyette BNR (2019). Sestd1 encodes a developmentally dynamic synapse protein that complexes with BCR Rac1-GAP to regulate forebrain dendrite, spine and synapse formation. Cerebral Cortex, 29(2): 505-516.
Minnella AM, Zhao JX, Jiang X, Jakobsen E, Lu F, Wu L, El-Benna J, Gray JA, and Swanson RA (2018). Excitotoxic superoxide production and neuronal death require both ionotropic and non-ionotropic NMDA receptor signaling, Scientific Reports, 8: 17522.
Sun W, Wong JM, Gray JA*, and Carter BC* (2018). Incomplete block of NMDA receptors by intracellular MK-801. Neuropharmacology, 143: 122-129. (*co-corresponding authors)
Wong JM and Gray JA (2018). Long-term depression is independent of GluN2 subunit composition. Journal of Neuroscience, 38(19): 4462-4470.
Ly C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson P, Burbach KF, Dunlap LE, Zarandi SS, Sood A, Paddy MR, Duim WC, Dennis MY, McAllister AK, Ori-McKenney KM, Gray JA, and Olson DE (2018). Psychedelics Promote Structural and Functional Neural Plasticity. Cell Reports, 23(11): 3170-3182.
Gray JA, Zito K, and Hell JW (2016). Non-ionotropic signaling by the NMDA receptor: controversy and opportunity. F1000Research, 5(F1000 Faculty Rev): 1010.
Stein IS, Gray JA, and Zito K (2015). Non-ionotropic NMDA receptor signaling drives activity-induced dendritic spine shrinkage. Journal of Neuroscience, 35(35): 12303-12308.
Gray JA (2015). Tardive Dyskinesia, in Ferri’s Clinical Advisor 2016. Ferri FF (Ed.), Mosbi, Philadelphia, PA, p 1198.
Gray JA and Nicoll RA (2014). Introduction to the Pharmacology of CNS Drugs, in Basic and Clinical Pharmacology. Katzung BG (Ed.), McGraw-Hill, New York, NY, pp 355-368.
Sanz-Clemente A, Gray JA, Nicoll RA, and Roche KW (2013). Activated CaMKII couples GluN2B and Casein Kinase 2 to control synaptic NMDA receptors. Cell Reports, 3(3): 607-614.
Gray JA and Nicoll RA (2012). Thinking outside the synapse: glycine at extrasynaptic NMDA receptors. Cell, 150(3): 455-456.
Chen BS*, Gray JA*, Sanz-Clemente A, Wei Z, Thomas EV, Nicoll RA, and Roche KW (2012). SAP102 mediates synaptic clearance of NMDA receptors. Cell Reports, 2(5): 1120-1128. (*co-first authors)
Gray JA (2012). Parkinsonism and rabbit syndrome following discontinuation of low-dose ziprasidone and concomitant initiation of sertraline. Journal of Clinical Psychopharmacology, 32(1): 142-143.
Gray JA, Shi Y, Usui H, During MJ, Sakimura K, Nicoll RA (2011). Distinct modes of AMPA receptor suppression at developing synapses by GluN2A and GluN2B: single-cell NMDA receptor subunit deletion in vivo. Neuron, 71(6): 1085-1101.
Lu W*, Gray JA*, Granger AJ, During MJ, Nicoll RA (2011). The potentiation of synaptic AMPA receptors induced by the deletion of NMDA receptors requires the GluA2 subunit. Journal of Neurophysiology, 105(2): 923-928. (*co-first authors)
Granger AJ, Gray JA, Lu W, and Nicoll RA (2011). Genetic analysis of neuronal ionotropic glutamate receptor subunits. Journal of Physiology, 589(17): 4095-4101.
Juge N, Gray JA, Omote H, Miyaji T, Inoue T, Hara C, Uneyama H, Edwards RH, Nicoll RA, Moriyama Y (2010). Metabolic control of vesicular glutamate transport and release. Neuron, 68(1): 99-112.
Gray JA and Risch SC (2009). When clozapine is not enough. Augment with lamotrigine? Current Psychiatry, 8(1): 41-46.
Berger M, Gray JA, and Roth BL (2009). The expanded biology of serotonin. Annual Review of Medicine, 60: 355-366.
Gray JA and Roth BL (2009). Intraneuronal Signaling, in Kaplan & Sadock's Comprehensive Textbook of Psychiatry. Sadock BJ, Sadock VA and Ruiz P (Eds.) Lippincott Williams & Wilkins, Philadelphia, PA, pp 118-129.
Gray JA and Roth BL (2007). The pipeline and future of drug development in schizophrenia. Molecular Psychiatry, 12(10): 904-922.
Gray JA and Roth BL (2007). Molecular targets for treating cognitive dysfunction in schizophrenia. Schizophrenia Bulletin, 33(5): 1100-1119.
Gray JA and Roth BL (2007). Serotonin Systems, in Handbook of Contemporary Neuropharmacology. Sibley DR, Hanin I, Kuhar M and Skolnick P (Eds.), John Wiley & Sons, New York, NY, pp 257-298.
Gray JA and Roth BL (2006). Developing selectively non-selective drugs for treating CNS disorders. Drug Discovery Today: Therapeutic Strategies, 3(4): 413-419.
Xia Z, Hufeisen SJ, Gray JA, and Roth BL (2003). The PDZ-binding domain is essential for the dendritic targeting of 5-HT2A serotonin receptors in cortical pyramidal neurons in vitro. Neuroscience, 122(4): 907-920.
Gray JA, Compton-Toth BA, and Roth BL (2003). Identification of two serine residues essential for agonist-induced 5-HT2A receptor desensitization. Biochemistry, 42(36): 10853-10862.
Xia Z, Gray JA, Compton-Toth BA, and Roth BL (2003). A direct interaction of PSD-95 with 5-HT2A serotonin receptors regulates receptor trafficking and signal transduction. Journal of Biological Chemistry 278(24): 21901-21908.
Gray JA, Bhatnagar A, Gurevich VV, and Roth BL (2003). The interaction of a constitutively active arrestin with the arrestin-insensitive 5-HT2A receptor induces agonist-independent internalization. Molecular Pharmacology 63(5): 961-972.
Gray JA and Roth BL (2002). A Last GASP for GPCRs? Science 297: 529-531.
Gray JA, Sheffler DJ, Bhatnagar A, Woods JA, Hufeisen SJ, Benovic JL, and Roth BL (2001). Cell-type specific effects of endocytosis inhibitors on 5-HT2A receptor desensitization and resensitization reveal an arrestin-, GRK2- and GRK5-independent mode of regulation in HEK-293 cells. Molecular Pharmacology 60(5): 1020-1030.
Gray JA and Roth BL (2001). Paradoxical trafficking and regulation of 5-HT2A receptors by agonists and antagonists. Brain Research Bulletin 56(5): 441-451.
Bhatnagar A, Willins DL, Gray JA, Woods JA, Benovic JL, and Roth BL (2001). The dynamin-dependent, arrestin-independent internalization of 5-hydroxytryptamine2A (5-HT2A) serotonin receptors reveals differential sorting of arrestins and 5-HT2A receptors during endocytosis. Journal of Biological Chemistry 276(11): 8269-8277.
Gelber EI, Kroeze WK, Willins DL, Gray JA, Sinar CA, Hyde EG, Gurevich V, Benovic JL, and Roth BL (1999). Structure and function of the third intracellular loop of the 5-hydroxytryptamine2A receptor: the third intracellular loop is alpha-helical and binds purified arrestins. Journal of Neurochemistry 72: 2206-2214.