J. Julius Zhu

Education

  • BS, Beijing University
  • MS, Shanghai Brain Research Institute
  • PhD, University of Wisconsin Medical School

Primary Appointment

  • Associate Professor, Pharmacology

Contact

Research Interest(s)

Neural circuit mechanisms of behavior and diseases

Research Description

My students and I are interested in central neural circuits and synapses. We enjoy developing new experimental approaches that combine cutting-edge techniques, including rapid recombinant DNA delivery and replacement, multiple whole-cell recordings, single- and two-photon microscopy-based optogenetics and imaging, and immunoelectron microscopy. These technologies allow us to decipher the molecular and cellular regulations (e.g., nanoscale Ras/MAPK signaling) of synapses in neural circuits, as well as the organization and functions (e.g., salience selection) of neural circuits. Genetic defects of many signaling molecules are linked to a number of cognitive disorders, e.g., Akt/PKB and calcineurin with schizophrenia, BRaf with cardio-facio-cutaneous syndrome, Brag/IQSec with nonsyndromic X-linked mental retardation, CaMKII with Angelman syndrome, H-Ras with Costello syndrome, p38MAPK and JNK with Alzheimer's disease, PI3K with fragile X syndrome, PTEN with autism, Cowden and Bannayan-Riley-Ruvalcaba syndromes, RasGap NF1 with neurofibromatosis, Rsk with Coffin-Lowry syndrome and X-linked mental retardation, SHP-2 with Noonan syndrome, and tuberin with tuberous sclerosis. Altered interneuronal function is a common mechanism contributing to various neurological, mental and psychiatric disorders, including autisms, epilepsy, depression, Huntington’s disease, neurofibromatosis, schizophrenia, Tourette’s syndrome and trauma. Therefore, the findings from our research should guide the future development of treatments for these insidious diseases.

Postdoctoral research associate position available, please contact: jjzhu@virginia.edu

Selected Publications

  • Lim C, Hoang E, Viar K, Stornetta R, Scott M, Zhu J. Pharmacological rescue of Ras signaling, GluA1-dependent synaptic plasticity, and learning deficits in a fragile X model. Genes & development. 2014;28(3): 273-89. PMID: 24493647
  • Wang G, Zhu J. DISC1 dynamically regulates synaptic N-methyl-D-aspartate responses in excitatory neurons. Biological psychiatry. 2014;75(5): 348-50. PMID: 24507569
  • Jiang X, Wang G, Lee A, Stornetta R, Zhu J. The organization of two new cortical interneuronal circuits. Nature neuroscience. 2013;16(2): 210-8. PMID: 23313910 | PMCID: PMC3589105
  • Myers K, Wang G, Sheng Y, Conger K, Casanova J, Zhu J. Arf6-GEF BRAG1 Regulates JNK-Mediated Synaptic Removal of GluA1-Containing AMPA Receptors: A New Mechanism for Nonsyndromic X-Linked Mental Disorder. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2012;32(34): 11716-26. PMID: 22915114 | PMCID: PMC3459061
  • Stornetta R, Zhu J. Ras and Rap signaling in synaptic plasticity and mental disorders. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry. 2010;17(1): 54-78. PMID: 20431046 | PMCID: PMC3119507
  • Activity level-dependent synapse-specific AMPA receptor trafficking regulates transmission kinetics. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2009;29(19): 6320-35. PMID: 19439609 | PMCID: PMC2734326
  • Kielland A, Bochorishvili G, Corson J, Zhang L, Rosin D, Heggelund P, Zhu J. Activity patterns govern synapse-specific AMPA receptor trafficking between deliverable and synaptic pools. Neuron. 2009;62(1): 84-101. PMID: 19376069 | PMCID: PMC2682220
  • Hu H, Qin Y, Bochorishvili G, Zhu Y, van Aelst L, Zhu J. Ras signaling mechanisms underlying impaired GluR1-dependent plasticity associated with fragile X syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2008;28(31): 7847-62. PMID: 18667617 | PMCID: PMC2553221
  • McCormack S, Stornetta R, Zhu J. Synaptic AMPA receptor exchange maintains bidirectional plasticity. Neuron. 2006;50(1): 75-88. PMID: 16600857
  • Qin Y, Zhu Y, Baumgart J, Stornetta R, Seidenman K, Mack V, van Aelst L, Zhu J. State-dependent Ras signaling and AMPA receptor trafficking. Genes & development. 2005;19(17): 2000-15. PMID: 16107614 | PMCID: PMC1199571
  • Zhu Y, Pak D, Qin Y, McCormack S, Kim M, Baumgart J, Velamoor V, Auberson Y, Osten P, van Aelst L, Sheng M, Zhu J. Rap2-JNK removes synaptic AMPA receptors during depotentiation. Neuron. 2005;46(6): 905-16. PMID: 15953419
  • Zhu Y, Stornetta R, Zhu J. Chandelier cells control excessive cortical excitation: characteristics of whisker-evoked synaptic responses of layer 2/3 nonpyramidal and pyramidal neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2004;24(22): 5101-8. PMID: 15175379
  • Zhu Y, Zhu J. Rapid arrival and integration of ascending sensory information in layer 1 nonpyramidal neurons and tuft dendrites of layer 5 pyramidal neurons of the neocortex. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2004;24(6): 1272-9. PMID: 14960597
  • Larkum M, Zhu J. Signaling of layer 1 and whisker-evoked Ca2+ and Na+ action potentials in distal and terminal dendrites of rat neocortical pyramidal neurons in vitro and in vivo. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2002;22(16): 6991-7005. PMID: 12177197
  • Zhu J, Qin Y, Zhao M, Van Aelst L, Malinow R. Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell. 2002;110(4): 443-55. PMID: 12202034
  • Lee A, Wang G, Jiang X, Johnson S, Hoang E, Lanté F, Stornetta R, Beenhakker M, Shen Y, Zhu J. Canonical organization of layer 1 neuron-led cortical inhibitory and disinhibitory interneuronal circuits Cerebral Cortex (Epub ahead of print). .