I, Dr. Guo-rong Zhang, have had a remarkable journey. I am from a small agricultural town about a day's drive south of Beijing, China. I worked my way up through the Chinese system, first at a provincial University and then in Beijing, obtaining both the M.D. and Ph.D. I then joined Dr. Geller's Laboratory at the W. Roxbury VA Hospital/Harvard Med. Schl. In July 2004, I was promoted to Instructor, a faculty level position. In Feb. 2004,1 received permanent residency status. I am intent on having an academic career in the US. I am skilled in neurosurgery and neuroanatomy, and have a broad overall knowledge of neuroscience. This proposal will provide training in molecular biology, virology, neuronal physiology, and learning and memory. Training includes coursework and a research program, emphasizing the new areas for me. This training should enable me to become an independent scientist and obtain NIH research grant (R01) support. Cognitive deficits are caused by aging, specific neurodegenerative diseases, stroke, and other conditions. No effective treatments are available. Gene therapy has tremendous potential for treating specific cognitive deficits. Learning theories hypothesize that neurons in a specific circuit use specific signaling pathways to modify synaptic strengths, thereby mediating learning. Thus, altering the physiology of a small group of neurons can potentiate a specific circuit and enhance learning, providing a treatment for cognitive deficits. I have established that genetic activation of protein kinase C (PKC) pathways in small groups of rat postrhinal cortex neurons enhances learning of visual object discriminations. PKC pathways were activated in several hundred predominantly glutamatergic and GABAergic neurons (using a Herpes Simplex Virus (HSV-1) vector that expresses a constitutively active PKC). Also, I showed that activating PKC pathways in small groups of hippocampal dentate granule neurons enhances learning of an auditory reversal discrimination, and, in aged rats, corrects deficits in a spatial learning. The long-term goal of this proposal is to develop a gene therapy treatment for cognitive deficits. The first specific aim will characterize correction of cognitive deficits in aged rats following activation of PKC pathways in small groups of hippocampal or postrhinal cortex neurons. The second specific aim will determine how long the recombinant PKC must be expressed to correct the learning deficits. ? ? ?

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Scientist Development Award - Research & Training (K01)
Project #
Application #
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Wagster, Molly V
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard University
Schools of Medicine
United States
Zip Code
Zhang, Guo-Rong; Zhao, Hua; Cook, Nathan et al. (2017) Characteristic and intermingled neocortical circuits encode different visual object discriminations. Behav Brain Res 331:261-275
Zhang, Guo-Rong; Zhao, Hua; Abdul-Muneer, P M et al. (2015) Neurons can be labeled with unique hues by helper virus-free HSV-1 vectors expressing Brainbow. J Neurosci Methods 240:77-88
Zhang, Guo-rong; Zhao, Hua; Cao, Haiyan et al. (2012) Targeted gene transfer of different genes to presynaptic and postsynaptic neocortical neurons connected by a glutamatergic synapse. Brain Res 1473:173-84
Zhang, Guo-Rong; Zhao, Hua; Choi, Eui M et al. (2012) CaMKII, MAPK, and CREB are coactivated in identified neurons in a neocortical circuit required for performing visual shape discriminations. Hippocampus 22:2276-89
Zhang, Guo-Rong; Zhao, Hua; Cao, Haiyan et al. (2012) Overexpression of either lysine-specific demethylase-1 or CLOCK, but not Co-Rest, improves long-term expression from a modified neurofilament promoter, in a helper virus-free HSV-1 vector system. Brain Res 1436:157-67
Zhang, Guo-Rong; Zhao, Hua; Li, Xu et al. (2011) A 16 bp upstream sequence from the rat tyrosine hydroxylase promoter supports long-term expression from a neurofilament promoter, in a helper virus-free HSV-1 vector system. Brain Res 1415:109-18
Cao, Haiyan; Zhang, Guo-rong; Geller, Alfred I (2011) Antibody-mediated targeted gene transfer of helper virus-free HSV-1 vectors to rat neocortical neurons that contain either NMDA receptor 2B or 2A subunits. Brain Res 1415:127-35
Zhang, Guo-rong; Li, Xu; Cao, Haiyan et al. (2011) The vesicular glutamate transporter-1 upstream promoter and first intron each support glutamatergic-specific expression in rat postrhinal cortex. Brain Res 1377:1-12
Zhang, Guo-rong; Cao, Haiyan; Kong, Lingxin et al. (2010) Identified circuit in rat postrhinal cortex encodes essential information for performing specific visual shape discriminations. Proc Natl Acad Sci U S A 107:14478-83
Zhang, Guo-rong; Geller, Alfred I (2010) A helper virus-free HSV-1 vector containing the vesicular glutamate transporter-1 promoter supports expression preferentially in VGLUT1-containing glutamatergic neurons. Brain Res 1331:12-9

Showing the most recent 10 out of 13 publications