J. Julius Zhu

Education

  • BS, Peking University
  • MS, Shanghai Brain Research Institute
  • PhD, University of Wisconsin Medical School
  • Postdoc, Max-Planck-Institut for Medical Research
  • Postdoc, Cold Spring Harbor Laboratory
  • Sabbatical, Norwegian University of Science & Technology

Primary Appointment

  • Associate Professor, Pharmacology

Contact

Research Interest(s)

Neural Circuits in Healthy and Diseased Brains

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 (Wang G, Wyskiel D, et al., Nature Protocols 10:397-412). 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 (Stornetta and Zhu, Neuroscientist 17: 54-78). Therefore, the findings from our research should guide the future development of treatments for these insidious diseases.

Selected Publications First-authored by Undergraduate Students: Sheng Y, Zhang L, Su S, Tsai LH and Zhu JJ (2015) Cdk5 is a new rapid homeostatic transmission regulator capable of inducing the early Alzheimer-like synaptic pathology. Cerebral Cortex [Epub ahead of print].

Lee AJ, Wang G, Jiang X, Johnson SM, Hoang ET, Lanté F, Stornetta RL, Beenhakker MP, Shen Y and Zhu JJ (2014) Canonical organization of layer 1 neuron-led cortical inhibitory and disinhibitory interneuronal circuits. Cerebral Cortex [Epub ahead of print].

Selected Publications First-authored by Graduate Students: Kielland A, Bochorishvili G, Corson J, Zhang L, Rosin DL, Heggelund P and Zhu JJ (2009) Activity patterns govern synapse-specific AMPA-R trafficking between deliverable and synaptic pools. Neuron 62:84-101.

McCormack SG, Stornetta RL and Zhu JJ (2006) Synaptic AMPA receptor exchange maintains bidirectional plasticity. Neuron 50:75-88.

Selected Publications by PI: Zhu JJ (2009) Activity level-dependent synapse-specific AMPA receptor trafficking regulates transmission kinetics. J Neurosci 29:6320-35.

Zhu JJ (2000) Maturation of layer 5 neocortical pyramidal neurons: amplifying salient layer 1 and layer 4 inputs by Ca2+ action potentials in adult rat tuft dendrites. J Physiol (Lond) 526:571-87.

Postdoctoral research associate, graduate and undergraduate student position available, please contact: jjzhu@virginia.edu

Selected Publications

  • Wang G, Bochorishvili G, Chen Y, Salvati K, Zhang P, Dubel S, Perez-Reyes E, Snutch T, Stornetta R, Deisseroth K, Erisir A, Todorovic S, Luo J, Kapur J, Beenhakker M, Zhu J. CaV3.2 calcium channels control NMDA receptor-mediated transmission: a new mechanism for absence epilepsy. Genes & development. 2015;29(14): 1535-51. PMID: 26220996
  • 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
  • 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
  • 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
  • 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, 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
  • Kolleker A, Zhu J, Schupp B, Qin Y, Mack V, Borchardt T, Köhr G, Malinow R, Seeburg P, Osten P. Glutamatergic plasticity by synaptic delivery of GluR-B(long)-containing AMPA receptors. Neuron. 2003;40(6): 1199-212. PMID: 14687553
  • 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, Malinow R. Acute versus chronic NMDA receptor blockade and synaptic AMPA receptor delivery. Nature neuroscience. 2002;5(6): 513-4. PMID: 11967548
  • 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
  • Zhu J, Esteban J, Hayashi Y, Malinow R. Postnatal synaptic potentiation: delivery of GluR4-containing AMPA receptors by spontaneous activity. Nature neuroscience. 2000;3(11): 1098-106. PMID: 11036266
  • Larkum M, Zhu J, Sakmann B. A new cellular mechanism for coupling inputs arriving at different cortical layers. Nature. 1999;398(6725): 338-41. PMID: 10192334
  • Zhu J, Connors B. Intrinsic firing patterns and whisker-evoked synaptic responses of neurons in the rat barrel cortex. Journal of neurophysiology. 1999;81(3): 1171-83. PMID: 10085344